MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Clinical Pharmacology and Therapeutics' source. Wed, 08 Feb 2012 14:04:06 +0100 http://www.medworm.com/index.php?rid=5627340&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261678%26dopt%3DAbstract Authors: PMID: 22261678 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627340 Wed, 25 Jan 2012 22:25:19 +0100 5627340 http://www.medworm.com/index.php?rid=5627339&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261679%26dopt%3DAbstract Authors: Miksys SL, Uhl K, Tyndale RF PMID: 22261679 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627339 Wed, 25 Jan 2012 22:25:09 +0100 5627339 http://www.medworm.com/index.php?rid=5627338&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261680%26dopt%3DAbstract Authors: PMID: 22261680 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627338 Wed, 25 Jan 2012 22:24:59 +0100 5627338 http://www.medworm.com/index.php?rid=5627337&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261681%26dopt%3DAbstract Authors: PMID: 22261681 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627337 Wed, 25 Jan 2012 22:24:49 +0100 5627337 http://www.medworm.com/index.php?rid=5627336&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261682%26dopt%3DAbstract Direct brain interventions to "treat" disfavored human behaviors: ethical and social issues. Clin Pharmacol Ther. 2012 Feb;91(2):163-5 Authors: Greely HT Abstract As neuroscience learns more about the causes of human behaviors, it will give us new ways to change those behaviors. When behaviors are caused by "brain diseases," effective actions that intervene directly in the brain will be readily accepted, but what about direct brain interventions that treat brain-based causes of socially disfavored behaviors that are not generally viewed as diseases? PMID: 22261682 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627336 Wed, 25 Jan 2012 22:24:40 +0100 5627336 http://www.medworm.com/index.php?rid=5627335&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261683%26dopt%3DAbstract Authors: Leon AC Abstract Comparative-effectiveness antidepressant trials offer promise to provide empirical evidence for clinicians choosing among interventions. Whether such trials posit superiority or noninferiority (NI) hypotheses, they pose formidable challenges. For instance, if meaningful antidepressant differences are seen in comparative-superiority trials, they will be small. NI hypothesis testing, on the other hand, requires an a priori NI margin and evidence of trial assay sensitivity. Either design demands unusually large samples, which could render such trials infeasible. PMID: 22261683 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627335 Wed, 25 Jan 2012 22:24:30 +0100 5627335 http://www.medworm.com/index.php?rid=5627334&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261684%26dopt%3DAbstract Authors: Artino AR, Durning SJ, Waechter DM, Leary KL, Gilliland WR Abstract The tendency to overestimate the influence of personal characteristics on outcomes, and to underestimate the influence of situational factors, is known as the fundamental attribution error. We argue that medical-education researchers and policy makers may be guilty of this error in their quest to understand clinical quality. We suggest that to truly understand clinical quality, they must examine situational factors, which often have a strong influence on the quality of clinical encounters. PMID: 22261684 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627334 Wed, 25 Jan 2012 22:24:20 +0100 5627334 http://www.medworm.com/index.php?rid=5627333&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261685%26dopt%3DAbstract Authors: Shuldiner AR Abstract Electronic health records (EHRs) coupled to DNA biobanks are potentially powerful but untested resources for pharmacogenomic discoveries. As described in this issue, Delaney and co-workers validated the use of EHRs by demonstrating that loss-of-function CYP2C19*2 was associated with poorer cardiovascular outcomes in clopidogrel-treated patients with an effect size similar to that reported in more controlled clinical trials. Whether studies from real-world EHR-biobanks will supplant randomized clinical trials to provide a sufficient evidence base to change practice is less certain. PMID: 22261685 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627333 Wed, 25 Jan 2012 22:24:11 +0100 5627333 http://www.medworm.com/index.php?rid=5627342&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22258468%26dopt%3DAbstract Authors: Kruhlak NL, Benz RD, Zhou H, Colatsky TJ Abstract The ability to predict clinical safety based on chemical structures is becoming an increasingly important part of regulatory decision making. (Quantitative) structure-activity relationship ((Q)SAR) models are currently used to evaluate late-arising safety concerns and possible nonclinical effects of a drug and its related compounds when adequate safety data are absent or equivocal. Regulatory use will likely increase with the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms. PMID: 22258468 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627342 Wed, 18 Jan 2012 05:00:00 +0100 5627342 http://www.medworm.com/index.php?rid=5627341&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22258469%26dopt%3DAbstract Authors: Tarning J, Zongo I, Somé FA, Rouamba N, Parikh S, Rosenthal PJ, Hanpithakpong W, Jongrak N, Day NP, White NJ, Nosten F, Ouedraogo JB, Lindegardh N Abstract Dihydroartemisinin-piperaquine is being increasingly used as a first-line artemisinin combination treatment for malaria. The aim of this study was to describe the pharmacokinetic and pharmacodynamic properties of piperaquine in 236 children with uncomplicated falciparum malaria in Burkina Faso. They received a standard body weight-based oral 3-day fixed-dose dihydroartemisinin-piperaquine regimen. Capillary plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling. The population pharmacokinetics of piperaquine were described accurately by a two-transit-compartment absorption model an... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5627341 Wed, 18 Jan 2012 05:00:00 +0100 5627341 http://www.medworm.com/index.php?rid=5607323&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22237256%26dopt%3DAbstract Authors: Daali Y, Samer C, Déglon J, Thomas A, Chabert J, Rebsamen M, Staub C, Dayer P, Desmeules J Abstract We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administratio... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5607323 Wed, 11 Jan 2012 05:00:00 +0100 5607323 http://www.medworm.com/index.php?rid=5607322&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22237257%26dopt%3DAbstract Authors: Yoon D, Park MY, Choi NK, Park BJ, Kim JH, Park RW Abstract Electronic health records (EHRs) are expected to be a good source of data for pharmacovigilance. However, current quantitative methods are not applicable to EHR data. We propose a novel quantitative postmarketing surveillance algorithm, the Comparison of Laboratory Extreme Abnormality Ratio (CLEAR), for detecting adverse drug reaction (ADR) signals from EHR data. The methodology involves calculating the odds ratio of laboratory abnormalities between a specific drug-exposed group and a matched unexposed group. Using a 10-year EHR data set, we applied the algorithm to test 470 randomly selected drug-event pairs. It was found possible to analyze a single drug-event pair in just 109 ± 159 seconds. In total, 120 of th... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5607322 Wed, 11 Jan 2012 05:00:00 +0100 5607322 http://www.medworm.com/index.php?rid=5568802&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22218072%26dopt%3DAbstract We present several examples of how imaging can answer some of these questions pertaining to the central nervous system (CNS) during the early phases of development of drugs to treat diseases involving the CNS. We also present an overview of the challenges and the potential of using and further qualifying imaging biomarkers for clinical trials. PMID: 22218072 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5568802 Wed, 04 Jan 2012 05:00:00 +0100 5568802 http://www.medworm.com/index.php?rid=5568801&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22218073%26dopt%3DAbstract Authors: Timsit S, Menn B PMID: 22218073 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5568801 Wed, 04 Jan 2012 05:00:00 +0100 5568801 http://www.medworm.com/index.php?rid=5568800&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22218074%26dopt%3DAbstract Authors: Meyer JH Abstract It is estimated that 15% of all individuals will experience a major depressive episode (MDE) during their lifetime and that treatment response is inadequate in 40% of these cases. To address this, neuroimaging is being used to identify MDE subtypes and mechanisms of onset as well as to optimize target occupancy of novel treatments. Neuroimaging of monoamine oxidase-A (MAO-A) binding; glutamate levels; indexes of 5-HT(2A), 5-HTT, 5-HT(1A), and 5-HT(1B) receptors; levels of dopamine transporters D(1) and D(2); and hippocampal volume are described here. Three themes emerge. First, symptoms such as pessimism, motor retardation, anxiety disorder, and verbal memory deficits best indicate the subtype of depression. Second, measures related to mechanisms of monoa... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5568800 Wed, 04 Jan 2012 05:00:00 +0100 5568800 http://www.medworm.com/index.php?rid=5539086&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22158568%26dopt%3DAbstract Authors: Lewiecki EM, Bilezikian JP Abstract Osteoporotic fractures and adverse skeletal effects of malignancies are associated with high bone turnover. Denosumab is a potent inhibitor of bone resorption with a novel mechanism of action. It is administered as an infrequent subcutaneous injection with no restrictions relating to renal function. This review summarizes data on the efficacy and safety of denosumab that led to its approval for the treatment of postmenopausal osteoporosis, cancer treatment-induced bone loss, and skeletal complications of malignancies. PMID: 22158568 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539086 Sun, 25 Dec 2011 12:32:51 +0100 5539086 http://www.medworm.com/index.php?rid=5539085&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22158569%26dopt%3DAbstract Authors: Langmuir PB, Yver A Abstract Vandetanib is a small-molecule inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET tyrosine kinases that has demonstrated clinical benefits in patients with medullary thyroid cancer (MTC). By identifying patients who are in greatest need of therapy, the risks of vandetanib can be balanced against the potential benefits in patients for whom there had been no effective therapy until now. This review discusses the development of vandetanib in patients with MTC and the benefits and risks in this patient population. PMID: 22158569 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539085 Sun, 25 Dec 2011 12:32:42 +0100 5539085 http://www.medworm.com/index.php?rid=5539084&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22166850%26dopt%3DAbstract Authors: Scott DL Abstract Rheumatoid arthritis (RA) remains a major clinical problem, but treatments involving biologics have revolutionized its management. They target pathogenically relevant cytokines such as tumor necrosis factor and immune cells such as B cells. In RA, biologics reduce joint inflammation, limit erosive damage, decrease disability, and improve quality of life. Infections are the main risk associated with their use. Because of the high prices of biologics, their cost-effectiveness is a matter of debate. They are mainly coadministered with disease-modifying drugs such as methotrexate when the latter are found to achieve insufficient disease control on their own. PMID: 22166850 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539084 Sun, 25 Dec 2011 12:32:32 +0100 5539084 http://www.medworm.com/index.php?rid=5539081&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179621%26dopt%3DAbstract Authors: PMID: 22179621 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539081 Sun, 25 Dec 2011 12:32:01 +0100 5539081 http://www.medworm.com/index.php?rid=5539080&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179622%26dopt%3DAbstract Authors: Waldman SA, Terzic A PMID: 22179622 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539080 Sun, 25 Dec 2011 12:31:51 +0100 5539080 http://www.medworm.com/index.php?rid=5539079&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179623%26dopt%3DAbstract Authors: PMID: 22179623 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539079 Sun, 25 Dec 2011 12:31:41 +0100 5539079 http://www.medworm.com/index.php?rid=5539078&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179624%26dopt%3DAbstract Authors: PMID: 22179624 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539078 Sun, 25 Dec 2011 12:31:30 +0100 5539078 http://www.medworm.com/index.php?rid=5539077&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179625%26dopt%3DAbstract Authors: Holstein SA, Hohl RJ Abstract Approval of agents for the treatment of cancers by the US Food and Drug Administration (FDA) was granted to only six new chemical entities in the three years spanning 2008 to 2010. By contrast, in the first nine months of 2011, six new chemical entities were approved for use in cancer. This approval rate is unprecedented and reflects the advances in science since the approval of the first monoclonal antibody (rituximab) in 1997 and the first targeted small-molecule tyrosine kinase inhibitor (imatinib) in 2001 for non-Hodgkin's lymphoma and chronic myelogenous leukemia, respectively. Here we briefly discuss the newly approved agents, a possible deletion from the therapeutic armamentarium, and the use of the FDA accelerated approval process. ... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539077 Sun, 25 Dec 2011 12:31:20 +0100 5539077 http://www.medworm.com/index.php?rid=5539076&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179626%26dopt%3DAbstract This report discusses the following aspects of biotech innovation: innovation in medicinal products, innovation in manufacturing processes, and innovation in regulatory science (both oversight and licensure). PMID: 22179626 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539076 Sun, 25 Dec 2011 12:31:10 +0100 5539076 http://www.medworm.com/index.php?rid=5539075&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179627%26dopt%3DAbstract Authors: PMID: 22179627 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539075 Sun, 25 Dec 2011 12:31:01 +0100 5539075 http://www.medworm.com/index.php?rid=5539074&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190063%26dopt%3DAbstract Authors: Delaney JT, Ramirez AH, Bowton E, Pulley JM, Basford MA, Schildcrout JS, Shi Y, Zink R, Oetjens M, Xu H, Cleator JH, Jahangir E, Ritchie MD, Masys DR, Roden DM, Crawford DC, Denny JC Abstract Variants in ABCB1 and CYP2C19 have been identified as predictors of cardiac events during clopidogrel therapy initiated after myocardial infarction (MI) or percutaneous coronary intervention (PCI). In addition, PON1 has recently been associated with stent thrombosis. The reported effects of these variants have not yet been replicated in a real-world setting. We used BioVU, the Vanderbilt DNA repository linked to de-identified electronic health records (EHRs), to find data on patients who were on clopidogrel treatment after an MI and/or a PCI; among these, we identified those who had e... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539074 Wed, 21 Dec 2011 05:00:00 +0100 5539074 http://www.medworm.com/index.php?rid=5539073&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190064%26dopt%3DAbstract We examined longitudinal pharmacokinetics (PK) data from a clinical trial of lopinavir/ritonavir (LPV/r) in HIV-infected infants in whom therapy was initiated at less than 6 months of age. A population PK analysis was performed using NONMEM to characterize changes in lopinavir (LPV) PK relating to maturational changes in infants, and to assess dosing requirements in this population. We also investigated the relationship between LPV PK and viral dynamic response. Age and ritonavir concentrations were the only covariates found to be significant. Population PK of LPV was characterized by high apparent clearance (CL/F) in young infants, which decreased with increasing age. Although younger infants had lower LPV concentrations, the viral dynamics did not correlate with initial LPV exposure. Mon... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539073 Wed, 21 Dec 2011 05:00:00 +0100 5539073 http://www.medworm.com/index.php?rid=5539072&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190065%26dopt%3DAbstract Authors: Butler K, Teng R Abstract During its development, ticagrelor, a drug designed to prevent thrombotic events in patients with acute coronary syndromes, was found to have an association with mild hyperuricemia. To investigate this effect further, we carried out a placebo-controlled, randomized, crossover study in 24 healthy male volunteers. The volunteers received ticagrelor (90 mg b.i.d. for 5 days), and serum uric acid and urinary uric acid excretion were assessed under strictly controlled conditions. After administration of ticagrelor, serum uric acid significantly increased (day 1: 4-6%; day 5: 4-10%) relative to placebo and rapidly returned to baseline after the last dose of the drug. Urinary uric acid excretion was significantly higher on day 1 (7%) and at 24-48 h after... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539072 Wed, 21 Dec 2011 05:00:00 +0100 5539072 http://www.medworm.com/index.php?rid=5539071&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190066%26dopt%3DAbstract Authors: Kasirye P, Kendall L, Adkison KK, Tumusiime C, Ssenyonga M, Bakeera-Kitaka S, Nahirya-Ntege P, Mhute T, Kekitiinwa A, Snowden W, Burger DM, Gibb DM, Walker AS Abstract The bioequivalence of formulations is usually evaluated in healthy adult volunteers. In our study in 19 HIV-1-infected Ugandan children (1.8-4 years of age, weight 12 to <15 kg) receiving zidovudine, lamivudine, and abacavir solutions twice a day for ≥24 weeks, the use of scored tablets allowed comparison of plasma pharmacokinetics of oral solutions vs. tablets. Samples were collected 0, 1, 2, 4, 6, 8, and 12 h after each child's last morning dose of oral solution before changing to scored tablets of Combivir (coformulated zidovudine + lamivudine) and abacavir; this was repeated 4 weeks later. Dose-norm... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539071 Wed, 21 Dec 2011 05:00:00 +0100 5539071 http://www.medworm.com/index.php?rid=5539070&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22190067%26dopt%3DAbstract Authors: Clarke TK, Weiss AR, Berrettini WH Abstract Anorexia nervosa (AN) is a disease defined by inappropriate weight loss and maintenance of body weight <85% of that expected for weight and height; it is most common in adolescent women aged 15-19 years. Numerous studies have highlighted the familial aggregation of the disease, suggesting a significant genetic component to its etiology. The purpose of this review is to discuss the different fields of genetic research-both in humans and animals-that have contributed to the understanding of this complex disorder. Candidate gene studies focusing on genes involved in the hypothalamic control of appetite and energy regulation have found genetic risk variants that increase risk for AN. A recent genome-wide association study has high... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539070 Wed, 21 Dec 2011 05:00:00 +0100 5539070 http://www.medworm.com/index.php?rid=5539083&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22166851%26dopt%3DAbstract Authors: Bauer M, Zeitlinger M, Karch R, Matzneller P, Stanek J, Jäger W, Böhmdorfer M, Wadsak W, Mitterhauser M, Bankstahl JP, Löscher W, Koepp M, Kuntner C, Müller M, Langer O Abstract Using positron emission tomography (PET) imaging we assessed, in vivo, the interaction between a microdose of (R)-[(11)C]verapamil (a P-glycoprotein (Pgp) substrate) and escalating doses of the Pgp inhibitor tariquidar (3, 4, 6, and 8 mg/kg) at the blood-brain barrier (BBB) in healthy human subjects. We compared the dose-response relationship of tariquidar in humans with data obtained in rats using a similar methodology. Tariquidar was equipotent in humans and rats in its effect of increasing (R)-[(11)C]verapamil brain uptake (expressed as whole-brain volume of distribution (V(T))), with very s... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539083 Wed, 14 Dec 2011 05:00:00 +0100 5539083 http://www.medworm.com/index.php?rid=5539082&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22166852%26dopt%3DAbstract Authors: Ober K, Benson S, Vogelsang M, Bylica A, Günther D, Witzke O, Kribben A, Engler H, Schedlowski M Abstract Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). During evocation, the subjects were reexposed to the CS alone. In responders (n = 15), the CS alone caused a significant inhibition of i... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5539082 Wed, 14 Dec 2011 05:00:00 +0100 5539082 http://www.medworm.com/index.php?rid=5428251&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089334%26dopt%3DAbstract Authors: PMID: 22089334 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428251 Sun, 20 Nov 2011 12:07:44 +0100 5428251 http://www.medworm.com/index.php?rid=5428250&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089335%26dopt%3DAbstract Authors: Smith B PMID: 22089335 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428250 Sun, 20 Nov 2011 12:07:35 +0100 5428250 http://www.medworm.com/index.php?rid=5428249&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089336%26dopt%3DAbstract Authors: PMID: 22089336 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428249 Sun, 20 Nov 2011 12:07:26 +0100 5428249 http://www.medworm.com/index.php?rid=5428248&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089337%26dopt%3DAbstract Authors: PMID: 22089337 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428248 Sun, 20 Nov 2011 12:07:17 +0100 5428248 http://www.medworm.com/index.php?rid=5428247&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089338%26dopt%3DAbstract Authors: Lalonde RL, Willke RJ Abstract Over the past 10 or more years, the drug development paradigm has shifted radically as a consequence of the availability of generic formulations for many important drugs and the growing influence of major payers in controlling reimbursement of new medicines. The demand for health care in an aging and increasingly information-seeking population is steadily outstripping society's ability to pay for all possible treatments. Regulatory approval of new drugs is necessary but no longer sufficient for market access in many countries, including the United States. PMID: 22089338 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428247 Sun, 20 Nov 2011 12:07:08 +0100 5428247 http://www.medworm.com/index.php?rid=5428246&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089339%26dopt%3DAbstract Authors: Hennessy S Abstract The demand for data from randomized comparative-effectiveness trials will always outstrip supply. Given their susceptibility to bias, several factors should be considered when examining nonrandomized comparative-effectiveness studies. These include comparability of treatments, magnitude of difference observed, sufficient attention to the underlying biology, examination of relationships supporting the main findings, whether the study includes only new users of the study treatments, whether the study end point is validly recorded, and replication of results. PMID: 22089339 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428246 Sun, 20 Nov 2011 12:06:58 +0100 5428246 http://www.medworm.com/index.php?rid=5428245&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089340%26dopt%3DAbstract Authors: Mandema JW, Gibbs M, Boyd RA, Wada DR, Pfister M Abstract High development cost, low development success, cost-disciplined health-care policies, and intense competition demand an efficient drug development process. New compounds need to bring value to patients by being safe, efficacious, and cost-effective as compared with existing treatment options. Model-based meta-analysis (MBMA) facilitates integration and utilization of summary-level efficacy and safety data, providing a quantitative framework for comparative efficacy and safety assessment.(1,2) This Commentary discusses the application and limitations of MBMA in drug development. PMID: 22089340 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428245 Sun, 20 Nov 2011 12:06:49 +0100 5428245 http://www.medworm.com/index.php?rid=5428244&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089341%26dopt%3DAbstract Authors: Ware MA Abstract The hazy world of "medical marijuana" continues to cry out for clear data on which to base medical decision making and rational policy design. In this issue of Clinical Pharmacology & Therapeutics, Abrams and colleagues report that vaporized cannabis does not meaningfully affect opioid plasma levels and may even augment the efficacy of oxycodone and morphine in patients with chronic non-cancer pain. This Commentary considers the implications of this work for clinical practice and further research initiatives. PMID: 22089341 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428244 Sun, 20 Nov 2011 12:06:40 +0100 5428244 http://www.medworm.com/index.php?rid=5428243&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089342%26dopt%3DAbstract Authors: Talameh JA, McLeod HL Abstract The antiplatelet drug clopidogrel is one of the most commonly prescribed drugs in the world, but there is wide interpatient variability in its antiplatelet effects. The majority of this variation is due to genetic effects, but there is controversy over which genetic variants are important and their relative contribution. This controversy may stem from the genetic association research paradigm, which casts the "winner's curse." PMID: 22089342 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428243 Sun, 20 Nov 2011 12:06:31 +0100 5428243 http://www.medworm.com/index.php?rid=5428242&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089343%26dopt%3DAbstract Authors: Bonello L, Bonello N, Grosdidier C, Camoin-Jau L Abstract Clopidogrel is an important antiplatelet agent, but a considerable variability in the biological effect of the drug has been observed. Additionally, patients with insufficient platelet reactivity inhibition following a loading dose (LD) of clopidogrel have a poor outcome. The mechanisms of variability are dependent on genetic polymorphisms of enzymes involved in clopidogrel metabolism. Paraoxonase 1 has been identified as the main determinant of the biological and clinical efficacy of clopidogrel. This finding could enable the use of pharmacogenomics to tailor antiplatelet agents. PMID: 22089343 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428242 Sun, 20 Nov 2011 12:06:21 +0100 5428242 http://www.medworm.com/index.php?rid=5428241&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089344%26dopt%3DAbstract Authors: PMID: 22089344 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428241 Sun, 20 Nov 2011 12:06:12 +0100 5428241 http://www.medworm.com/index.php?rid=5428254&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089266%26dopt%3DAbstract Authors: Goyal N, Gomeni R Abstract The fact that there are high dropout rates in clinical trials of antipsychotic medications raises critical questions regarding the most appropriate method of designing new trials, analyzing efficacy data, and evaluating the clinical utility (CU) of novel treatments. In this article, we consider the use of a model-based approach to define an integrated CU criterion for better characterizing the clinical response to a treatment, for optimizing proof-of-concept trials, and for providing differentiating criteria for novel medications when complete information is not available. PMID: 22089266 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428254 Wed, 16 Nov 2011 05:00:00 +0100 5428254 http://www.medworm.com/index.php?rid=5428253&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089267%26dopt%3DAbstract Authors: Dani C, Vangi V, Bertini G, Pratesi S, Lori I, Favelli F, Ciuti R, Bandinelli A, Martano C, Murru P, Messner H, Schena F, Mosca F Abstract Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persisten... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428253 Wed, 16 Nov 2011 05:00:00 +0100 5428253 http://www.medworm.com/index.php?rid=5428252&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089268%26dopt%3DAbstract Authors: Beltrami AP, Cesselli D, Beltrami CA Abstract The term "cellular senescence" denotes a cellular response to several stressors that results in irreversible growth arrest, alterations of the gene expression profile, epigenetic modifications, and an altered secretome, all of which eventually impair the reparative properties of primitive cells, adding a layer of complexity to the field of regenerative medicine. The purpose of this review is to illustrate how cellular senescence could affect tissue repair and to propose interventions that aim at interfering with it. PMID: 22089268 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428252 Wed, 16 Nov 2011 05:00:00 +0100 5428252 http://www.medworm.com/index.php?rid=5428255&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22071696%26dopt%3DAbstract Authors: Camilleri M PMID: 22071696 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5428255 Wed, 09 Nov 2011 05:00:00 +0100 5428255 http://www.medworm.com/index.php?rid=5383489&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048219%26dopt%3DAbstract Authors: Guise JM, Viswanathan M PMID: 22048219 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383489 Wed, 02 Nov 2011 04:00:00 +0100 5383489 http://www.medworm.com/index.php?rid=5383488&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048220%26dopt%3DAbstract Authors: Pickard AS, Lee TA, Solem CT, Joo MJ, Schumock GT, Krishnan JA Abstract A major priority for funding agencies and researchers involved in comparative-effectiveness research (CER) is to ensure that research questions will produce findings that are relevant and feasible to implement. In this article, we describe a process for involving experts and stakeholders in identifying and prioritizing CER studies, as illustrated by our experience in chronic obstructive pulmonary disease (COPD). PMID: 22048220 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383488 Wed, 02 Nov 2011 04:00:00 +0100 5383488 http://www.medworm.com/index.php?rid=5383487&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048221%26dopt%3DAbstract Authors: Gurbel PA, Bliden KP, Fort J, Zhang Y, Plachetka JR, Antonino M, Gesheff M, Tantry US Abstract PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate-release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval ≤10% for the difference in least-square means of pla... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383487 Wed, 02 Nov 2011 04:00:00 +0100 5383487 http://www.medworm.com/index.php?rid=5383486&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048222%26dopt%3DAbstract Authors: Nakashima K, Narukawa M, Takeuchi M Abstract Drug development in Japan is shifting from a bridging strategy to a global strategy, and the number of multiregional trials in which Japan is included is increasing every year. The Japanese drug regulatory authority requires that data be collected in Japanese populations, and therefore dose-response studies of various drugs are frequently conducted in Japan. However, the current standard for adequate dose-finding processes may sometimes hinder the timely participation of Japan in these multiregional trials. We studied the development approaches and review patterns of 99 new molecular entities (NMEs) approved in 2003-2008 and have identified some common factors that result in differences in approved dosages in Japan as compared w... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383486 Wed, 02 Nov 2011 04:00:00 +0100 5383486 http://www.medworm.com/index.php?rid=5383485&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048223%26dopt%3DAbstract This study adds to the growing appreciation of flavonoid metabolites as bioactive compounds. PMID: 22048223 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383485 Wed, 02 Nov 2011 04:00:00 +0100 5383485 http://www.medworm.com/index.php?rid=5383484&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048224%26dopt%3DAbstract This study demonstrated that fluconazole alters formation of MDZ metabolites, both in vivo and in vitro, in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions among MDZ, CYP3A4/5, and other putative effectors. PMID: 22048224 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383484 Wed, 02 Nov 2011 04:00:00 +0100 5383484 http://www.medworm.com/index.php?rid=5383483&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048225%26dopt%3DAbstract Authors: Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL Abstract Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383483 Wed, 02 Nov 2011 04:00:00 +0100 5383483 http://www.medworm.com/index.php?rid=5383482&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048226%26dopt%3DAbstract Authors: Chain AS, Krudys KM, Danhof M, Della Pasqua O Abstract Early in the course of clinical development of new non-antiarrhythmic drugs, it is important to assess the propensity of these drugs to prolong the QT/QTc-interval. The current regulatory guidelines suggest using the largest time-matched mean difference between drug and placebo (baseline-adjusted) groups over the sampling interval, thereby neglecting any potential exposure-effect relationship and nonlinearity in the underlying physiological fluctuation in QT values. Thus far, most of the attempted models for characterizing drug-induced QTc-interval prolongation have disregarded the possibility of model parameterization in terms of drug-specific and system-specific properties. Using a database consisting of three compou... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383482 Wed, 02 Nov 2011 04:00:00 +0100 5383482 http://www.medworm.com/index.php?rid=5383481&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048227%26dopt%3DAbstract We present a dose-response meta-analysis to quantify relative efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). There is a strong rationale for this analysis because, although multiple biologics are available, information on head-to-head comparisons is limited. Data on the percentage of patients attaining American College of Rheumatology (ACR) 20, 50, and 70 responses were extracted from 50 randomized controlled trials representing 21,500 patients, five mechanisms of action, and nine biologics. The analysis showed that all tumor necrosis factor inhibitors (anti-TNFs) share the same dose-response relationship for ACR 20, 50, and 70, differing only in potency. Yet there are significant differences in efficacy among the anti-TNFs d... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383481 Wed, 02 Nov 2011 04:00:00 +0100 5383481 http://www.medworm.com/index.php?rid=5383480&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048228%26dopt%3DAbstract Authors: Brass EP, Lofstedt R, Renn O Abstract Nonprescription drugs pose unique challenges to regulators. The fact that the barriers to access are lower for nonprescription drugs as compared with prescription drugs may permit additional consumers to obtain effective drugs. However, the use of these drugs by consumers in the absence of supervision by a health-care professional may result in unacceptable rates of misuse and suboptimal clinical outcomes. A value-tree method is proposed that defines important benefit and risk domains relevant to nonprescription drugs. This value tree can be used to comprehensively identify product-specific attributes in each domain and can also support formal benefit-risk assessment using a variety of tools. This is illustrated here, using a modificat... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383480 Wed, 02 Nov 2011 04:00:00 +0100 5383480 http://www.medworm.com/index.php?rid=5383479&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048229%26dopt%3DAbstract This article attempts to describe the advances in (and the challenges of) validation of GGDPS as a novel therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. PMID: 22048229 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383479 Wed, 02 Nov 2011 04:00:00 +0100 5383479 http://www.medworm.com/index.php?rid=5383478&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048230%26dopt%3DAbstract Authors: Schneeweiss S, Gagne JJ, Glynn RJ, Ruhl M, Rassen JA Abstract Comparative-effectiveness research (CER) aims to produce actionable evidence regarding the effectiveness and safety of medical products and interventions as they are used outside of controlled research settings. Although CER evidence regarding medications is particularly needed shortly after market approval, key methodological challenges include (i) potential bias due to channeling of patients to the newly marketed medication because of various patient-, physician-, and system-related factors; (ii) rapid changes in the characteristics of the user population during the early phase of marketing; and (iii) lack of timely data and the often small number of users in the first few months of marketing. We propose a mix... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383478 Wed, 02 Nov 2011 04:00:00 +0100 5383478 http://www.medworm.com/index.php?rid=5383477&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048231%26dopt%3DAbstract Authors: Mandema JW, Boyd RA, Dicarlo LA Abstract Information on the comparative effectiveness of drugs is crucial for drug development decisions, in addition to being needed by regulators, prescribers, and payers. We have carried out a dose-response meta-analysis of three end points each for efficacy and bleeding for various anticoagulants evaluated for the prevention of venous thromboembolism (VTE) following orthopedic surgery to assess the comparative efficacy and safety of various classes of agents. Data obtained from 89 randomized controlled trials of 23 anticoagulants representing seven drug classes were analyzed. The analysis showed significant differences in the therapeutic index (TI), the ratio of the dose with an acceptable bleeding risk to the dose with a relevant risk r... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383477 Wed, 02 Nov 2011 04:00:00 +0100 5383477 http://www.medworm.com/index.php?rid=5383476&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22048232%26dopt%3DAbstract Authors: Greevy RA, Huizinga MM, Roumie CL, Grijalva CG, Murff H, Liu X, Griffin MR Abstract Two important challenges are inherent in the design of studies using prescription data from electronic health records: how to define the minimum level of adherence that would qualify as "continuous drug use" and how to handle stockpiling of medications. Generally, the sensitivity of a study's conclusions to these design choices is not analyzed. In our study, covariate adjusted Cox models were used to compare persistence and durability with respect to three common oral antidiabetic therapies in a cohort of 12,697 incident users. Assuming 50% stockpiling, sulfonylurea therapy, as compared with metformin, showed a significantly lower risk of nonpersistence (changing or stopping therapy) when n... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383476 Wed, 02 Nov 2011 04:00:00 +0100 5383476 http://www.medworm.com/index.php?rid=5383508&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975345%26dopt%3DAbstract Authors: Rothrock NE, Kaiser KA, Cella D PMID: 21975345 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383508 Tue, 01 Nov 2011 04:00:00 +0100 5383508 http://www.medworm.com/index.php?rid=5383507&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975346%26dopt%3DAbstract Authors: Rief W, Bingel U, Schedlowski M, Enck P PMID: 21975346 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383507 Tue, 01 Nov 2011 04:00:00 +0100 5383507 http://www.medworm.com/index.php?rid=5383506&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975347%26dopt%3DAbstract Authors: Pickering G, Schneider E, Papet I, Pujos-Guillot E, Pereira B, Simen E, Dubray C, Schoeffler P Abstract Patients undergoing major surgery represent a good model for the study of the hepatic metabolism of acetaminophen (APAP) after surgery and for the evaluation of how the detoxification process is influenced by aging. Thirty patients received intravenous APAP (1 g/6 h) for 4 days (D1-D4). Daily 24-h urinary metabolites-cysteine-APAP, mercapturate-APAP, APAP, and glucuronide and sulfate conjugates-as well as blood glutathione levels were compared with repeated-measures analysis of variance (significance, P < 0.05). Between D1 and D4, cysteine-APAP increased (308 ± 308 mg vs. 570 ± 512 mg, P = 0.005), and sulfate and glucuronide conjugates decreased (1,365 ± 1,084 mg v... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383506 Tue, 01 Nov 2011 04:00:00 +0100 5383506 http://www.medworm.com/index.php?rid=5383505&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975348%26dopt%3DAbstract Authors: Katz LB, Gambale JJ, Rothenberg PL, Vanapalli SR, Vaccaro N, Xi L, Polidori DC, Vets E, Sarich TC, Stein PP Abstract The incidence of type 2 diabetes mellitus is increasing worldwide. Several G-protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The ... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383505 Tue, 01 Nov 2011 04:00:00 +0100 5383505 http://www.medworm.com/index.php?rid=5383504&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975349%26dopt%3DAbstract Authors: Mestres J, Seifert SA, Oprea TI Abstract The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use. PMID: 21975349 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383504 Tue, 01 Nov 2011 04:00:00 +0100 5383504 http://www.medworm.com/index.php?rid=5383503&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975350%26dopt%3DAbstract Authors: Desta Z, Kreutz Y, Nguyen AT, Li L, Skaar T, Kamdem LK, Henry NL, Hayes DF, Storniolo AM, Stearns V, Hoffmann E, Tyndale RF, Flockhart DA Abstract The associations between plasma letrozole concentrations and CYP2A6 and CYP3A5 genetic variants were tested in the Exemestane and Letrozole Pharmacogenomics (ELPH) trial. ELPH is a multicenter, open-label prospective clinical trial in women randomly assigned (n ≈ 250 in each arm) to receive 2 years of treatment with either oral letrozole (2.5 mg/day) or oral exemestane (25 mg/day). CYP2A6 and CYP3A showed effects on letrozole metabolism in vitro. DNA samples were genotyped for variants in the CYP2A6 and CYP3A5 genes. Plasma letrozole concentrations showed high interpatient variability (>10-fold) and were associated signific... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383503 Tue, 01 Nov 2011 04:00:00 +0100 5383503 http://www.medworm.com/index.php?rid=5383502&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993424%26dopt%3DAbstract Authors: Hróbjartsson A, Boutron I Abstract Blinding, or "masking," is a crucial method for reducing bias in randomized clinical trials. In this paper, we review important methodological aspects of blinding, emphasizing terminology, reporting, bias mechanisms, empirical evidence, and the risk of unblinding. Theoretical considerations and empirical analyses support the blinding of patients, health-care providers, and outcome assessors as to the trial intervention to which patients have been allocated. We encourage extensive pretrial testing of blinding procedures and explicit reporting of who was in the blinded condition and the methods used to ensure blinding. PMID: 21993424 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383502 Tue, 01 Nov 2011 04:00:00 +0100 5383502 http://www.medworm.com/index.php?rid=5383501&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993425%26dopt%3DAbstract Authors: Benedetti F, Carlino E, Pollo A Abstract In placebo-controlled trials, the placebo component of treatments is usually assessed by simulating a therapy through the administration of a dummy treatment (placebo) in order to eliminate the specific effects of the therapy. Recently, a radically different approach to the analysis of placebo responses has been implemented in which placebo responses are assessed without placebo groups. To do this, the placebo (psychological) component is eliminated by conducting hidden (unexpected) administrations of the active treatment. Compelling experimental evidence now shows that when the psychological component is eliminated through the administration of therapies unbeknownst to the patient, the effects of a variety of treatments are signifi... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383501 Tue, 01 Nov 2011 04:00:00 +0100 5383501 http://www.medworm.com/index.php?rid=5383500&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993426%26dopt%3DAbstract In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy. PMID: 21993426 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383500 Tue, 01 Nov 2011 04:00:00 +0100 5383500 http://www.medworm.com/index.php?rid=5383499&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993427%26dopt%3DAbstract Authors: Hartling L, Wittmeier KD, Caldwell PH, van der Lee JH, Klassen TP, Craig JC, Offringa M Abstract Standards for Research in (StaR) Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic "knowledge to action" plan, StaR Child Health will make efforts to improve and expand the evidence base for child health across the world. PMID: 21993427 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383499 Tue, 01 Nov 2011 04:00:00 +0100 5383499 http://www.medworm.com/index.php?rid=5383498&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993428%26dopt%3DAbstract Authors: Coons SJ, Kothari S, Monz BU, Burke LB Abstract The importance of appropriately and effectively incorporating the patient's voice into the evaluation of new medical products has been recognized and affirmed by regulators.(1,2,3) Patient-reported outcomes (PROs) are increasingly being assessed in clinical trials to quantify treatment benefits such as symptom relief and improved functioning. Translating PRO-based treatment benefits into labeling claims can provide information to physicians and patients and assist in prescribing decisions.(4,5) Hence, standardizing the valid and reliable measurement of PRO end points is critical. PMID: 21993428 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383498 Tue, 01 Nov 2011 04:00:00 +0100 5383498 http://www.medworm.com/index.php?rid=5383497&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012306%26dopt%3DAbstract Authors: PMID: 22012306 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383497 Tue, 01 Nov 2011 04:00:00 +0100 5383497 http://www.medworm.com/index.php?rid=5383496&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012307%26dopt%3DAbstract Authors: PMID: 22012307 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383496 Tue, 01 Nov 2011 04:00:00 +0100 5383496 http://www.medworm.com/index.php?rid=5383495&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012308%26dopt%3DAbstract Authors: Ito S PMID: 22012308 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383495 Tue, 01 Nov 2011 04:00:00 +0100 5383495 http://www.medworm.com/index.php?rid=5383494&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012309%26dopt%3DAbstract Authors: PMID: 22012309 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383494 Tue, 01 Nov 2011 04:00:00 +0100 5383494 http://www.medworm.com/index.php?rid=5383493&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012310%26dopt%3DAbstract Authors: Abernethy DR, Bai JP, Burkhart K, Xie HG, Zhichkin P Abstract The rapid evolution of large biological, pharmacological, and chemical databases has led to optimism that such data resources can be leveraged for prediction of drug action based on molecular descriptors of the drug. Challenges to realize this possibility include organization of each type of database in a manner that allows extraction of information across disparate data sources and the linkage of information across the biological, pharmacological, and chemical domains. PMID: 22012310 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383493 Tue, 01 Nov 2011 04:00:00 +0100 5383493 http://www.medworm.com/index.php?rid=5383492&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012311%26dopt%3DAbstract Authors: Savitz DA Abstract Mandatory registration of observational studies has been proposed to enhance quality of published research and reduce selective publication of positive findings. Enhanced communication of study plans would be welcome, but the alleged benefits to research quality are illusory. In particular, prespecification of hypotheses has no independent effect on data quality or the likelihood that hypotheses are correct. Registration of studies and hypotheses is likely to be misinterpreted as an independent determinant of validity. PMID: 22012311 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383492 Tue, 01 Nov 2011 04:00:00 +0100 5383492 http://www.medworm.com/index.php?rid=5383491&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22012312%26dopt%3DAbstract We report the development of a novel pharmacogenetics-based 3-day warfarin initiation dose (ID) algorithm based on the International Warfarin Pharmacogenetics Consortium (IWPC) maintenance dose algorithm and the CYP2C9 genotype-based variance in warfarin half-life. The predictive value of the pharmacogenetics-based ID was assessed in a large cohort of 671 newly diagnosed patients with thromboembolic disorders who were about to commence anticoagulation therapy in accordance with standard induction regimens. In patients with mean international normalized ratio (INR)(days 4-7) >4.0 (n = 63) after warfarin initiation, the pharmacogenetics-based ID algorithm predicted a markedly lower dose requirement (median reduction = 4.2 mg), whereas in those with mean INR(days 4-7) <2.0 (n = 145), th... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383491 Tue, 01 Nov 2011 04:00:00 +0100 5383491 http://www.medworm.com/index.php?rid=5383490&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030567%26dopt%3DAbstract Authors: Toh S, Platt R, Steiner JF, Brown JS Abstract Comparative-effectiveness research (CER) can be conducted within a distributed health data network. Such networks allow secure access to separate data sets from different data partners and overcome many practical obstacles related to patient privacy, data security, and proprietary concerns. A scalable network architecture supports a wide range of CER activities and meets the data infrastructure needs envisioned by the Federal Coordinating Council for Comparative Effectiveness Research. PMID: 22030567 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5383490 Wed, 26 Oct 2011 04:00:00 +0100 5383490 http://www.medworm.com/index.php?rid=5284290&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934715%26dopt%3DAbstract Authors: PMID: 21934715 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284290 Sat, 01 Oct 2011 04:00:00 +0100 5284290 http://www.medworm.com/index.php?rid=5284289&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934716%26dopt%3DAbstract Authors: Waldman SA, Terzic A PMID: 21934716 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284289 Sat, 01 Oct 2011 04:00:00 +0100 5284289 http://www.medworm.com/index.php?rid=5284288&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934717%26dopt%3DAbstract Authors: PMID: 21934717 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284288 Sat, 01 Oct 2011 04:00:00 +0100 5284288 http://www.medworm.com/index.php?rid=5284287&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934718%26dopt%3DAbstract Authors: PMID: 21934718 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284287 Sat, 01 Oct 2011 04:00:00 +0100 5284287 http://www.medworm.com/index.php?rid=5284286&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934719%26dopt%3DAbstract Authors: Benowitz NL Abstract Smokeless tobacco (ST) delivers nicotine in doses similar to those received in cigarette smoking but does not expose the user to the toxic combustion gases and particles that are responsible for most tobacco-induced disease. This Opinion piece discusses the controversies pertaining to ST and health, the pros and cons of ST in harm reduction, and progress in treatment for those who would like to quit ST use. PMID: 21934719 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284286 Sat, 01 Oct 2011 04:00:00 +0100 5284286 http://www.medworm.com/index.php?rid=5284285&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934720%26dopt%3DAbstract Authors: Pereira NL, Weinshilboum RM Abstract Pharmacogenomics promises to help maximize efficacy and minimize adverse drug reactions. It could have a significant impact on the treatment of cardiovascular disease, the leading cause of death in the United States. The past decade has seen pharmacogenomics move from study of a candidate gene to genome-wide approaches, with the development of a series of pharmacogenetic tests. However, many barriers need to be overcome for cardiovascular pharmacogenomics to have its promised clinical impact. PMID: 21934720 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284285 Sat, 01 Oct 2011 04:00:00 +0100 5284285 http://www.medworm.com/index.php?rid=5284284&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934721%26dopt%3DAbstract Authors: Landstrom AP, Ackerman MJ Abstract Although the etiologies of sudden cardiac death (SCD) are diverse, genetic mutations associated with cardiomyopathic and channelopathic diseases are major causes, and clinically available genetic tests offer the potential to identify at-risk family members, contribute to risk stratification, and guide therapeutic intervention. Recently, the first large-scale systematic studies exploring the background genetic "noise" rate of these tests have been conducted and offer guidance in interpreting positive genetic test results. PMID: 21934721 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284284 Sat, 01 Oct 2011 04:00:00 +0100 5284284 http://www.medworm.com/index.php?rid=5284283&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934722%26dopt%3DAbstract Authors: Penn MS, Dong F, Klein S, Mayorga ME Abstract The field of cardiovascular regenerative medicine has made significant strides over the past decade. Clinical trials have demonstrated benefit in acute myocardial infarction (AMI) and chronic heart failure (CHF). As the field has matured, it has defined novel biology and invented an array of therapeutic strategies that are currently under development. In this brief review, we attempt to conceptualize the knowledge to date as well as examine how this knowledge has been translated to various therapeutic strategies. PMID: 21934722 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284283 Sat, 01 Oct 2011 04:00:00 +0100 5284283 http://www.medworm.com/index.php?rid=5284282&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21934723%26dopt%3DAbstract Authors: Potpara TS, Lip GY Abstract Atrial fibrillation (AF) confers an increased risk of ischemic stroke or thromboembolism that is reduced by long-term oral anticoagulant therapy. Until recently, the latter has typically been one from the vitamin K antagonist (VKA) class of drugs. Although highly effective, VKAs have limitations, and their use is challenging for both patients and clinicians. A new generation of oral anticoagulant drugs is emerging, including several drugs that appear to be viable alternatives to VKAs in AF patients. PMID: 21934723 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284282 Sat, 01 Oct 2011 04:00:00 +0100 5284282 http://www.medworm.com/index.php?rid=5284280&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21956616%26dopt%3DAbstract Response to "Commercial Factors Override Science in Combination Addiction Drug Trial" Clin Pharmacol Ther. 2011 Sep 28; Authors: Strain EC, Harrison JA, Bigelow GE PMID: 21956616 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284280 Wed, 28 Sep 2011 04:00:00 +0100 5284280 http://www.medworm.com/index.php?rid=5284279&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21956617%26dopt%3DAbstract Authors: Byrne A PMID: 21956617 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284279 Wed, 28 Sep 2011 04:00:00 +0100 5284279 http://www.medworm.com/index.php?rid=5284278&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21956618%26dopt%3DAbstract In this study, we characterized genetic variants of MATE2-K, determined their association with metformin response, and elucidated their impact by means of a comparative protein structure model. Four nonsynonymous variants and four variants in the MATE2-K basal promoter region were identified from ethnically diverse populations. Two nonsynonymous variants-c.485C>T and c.1177G>A-were shown to be associated with significantly lower metformin uptake and reduction in protein expression levels. MATE2-K basal promoter haplotypes containing the most common variant, g.-130G>A (>26% allele frequency), were associated with a significant increase in luciferase activities and reduced binding to the transcriptional repressor myeloid zinc finger 1 (MZF-1). Patients with diabetes who were homo... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284278 Wed, 28 Sep 2011 04:00:00 +0100 5284278 http://www.medworm.com/index.php?rid=5284281&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21937987%26dopt%3DAbstract Authors: Katzenmaier S, Markert C, Riedel KD, Burhenne J, Haefeli W, Mikus G Abstract We established a new limited sampling strategy to assess CYP3A activity and evaluated the time course of reversible (voriconazole) and irreversible (ritonavir) CYP3A inhibition. In this randomized trial, two groups, each with eight healthy participants, received CYP3A inhibitors voriconazole or ritonavir orally for 9 days, with 3 mg midazolam (MDZ) administered before the inhibitor treatment, on days 1, 2, 3, 5, 8, and 9 during inhibitor treatment, and on days 10, 11, and 12 (3 days) after discontinuation. Plasma MDZ area under the curve (AUC) between 2 and 4 h after oral administration in the form of a solution strongly correlated with MDZ clearance. Using this parameter, maximum inhibition of vo... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5284281 Wed, 21 Sep 2011 04:00:00 +0100 5284281 http://www.medworm.com/index.php?rid=5235220&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918509%26dopt%3DAbstract Authors: Johnson JA, Cavallari LH, Beitelshees AL, Lewis JP, Shuldiner AR, Roden DM Abstract The past decade has seen substantial advances in cardiovascular pharmacogenomics. Genetic determinants of response to clopidogrel and warfarin have been defined, resulting in changes to the product labels for these drugs that suggest the use of genetic information as a guide for therapy. Genetic tests are available, as are guidelines for incorporation of genetic information into patient-care decisions. These guidelines and the literature supporting them are reviewed herein. Significant advances have also been made in the pharmacogenomics of statin-induced myopathy and the response to β-blockers in heart failure, although the clinical applications of these findings are less clear. Other are... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5235220 Wed, 14 Sep 2011 04:00:00 +0100 5235220 http://www.medworm.com/index.php?rid=5235219&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918510%26dopt%3DAbstract Authors: Simon T, Steg PG, Becquemont L, Verstuyft C, Kotti S, Schiele F, Ferrari E, Drouet E, Grollier G, Danchin N Abstract Paraoxonase-1 (PON1) Q192R polymorphism was recently suggested to determine per se clopidogrel response on major cardiovascular events (MACEs). We assessed the impact of PON1, CYP2C19, and ABCB1 polymorphisms on MACE in clopidogrel-treated acute myocardial infarction (AMI) patients (N = 2,210), including those undergoing percutaneous coronary intervention (PCI) (n = 1,538). PON1 polymorphism was not associated with increased risk of in-hospital death and MACEs at 1 year (adjusted hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.66-1.61 and adjusted HR 0.77, 95% CI 0.42-1.41 for QQ versus RR in all and PCI patients, respectively). The presence of two CY... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5235219 Wed, 14 Sep 2011 04:00:00 +0100 5235219 http://www.medworm.com/index.php?rid=5221717&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21914835%26dopt%3DAbstract Authors: Okada R, Maeda K, Nishiyama T, Aoyama S, Tozuka Z, Hiratsuka A, Ikeda T, Kusuhara H, Sugiyama Y Abstract Null mutation of both glutathione S-transferase (GST) M1 and GSTT1 was reported to correlate statistically with an abnormal increase in the plasma levels of ALT or AST caused by troglitazone in the diabetic patients (Watanabe I et al., Clin Pharmacol Ther, 73, 435-55 (2003)). This clinical evidence leads to the hypothesis whereby glutathione (GSH) conjugation catalyzed by GSTT1 and GSTM1 has a role in the elimination of reactive metabolites of troglitazone. However, the contribution of GST isoforms expressed in human liver to the detoxification of reactive metabolites of troglitazone has not yet been clarified. We investigated the involvement of human GST isoforms in GS... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221717 Tue, 13 Sep 2011 04:00:00 +0100 5221717 http://www.medworm.com/index.php?rid=5221723&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900887%26dopt%3DAbstract In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction. PMID: 21900887 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221723 Wed, 07 Sep 2011 04:00:00 +0100 5221723 http://www.medworm.com/index.php?rid=5221722&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900888%26dopt%3DAbstract Authors: Malliaras K, Kreke M, Marbán E Abstract Stem cell therapy has emerged as a potential therapeutic strategy for myocardial infarction (MI). Multiple cell types used to regenerate the injured heart have been tested in clinical trials. The results of studies of skeletal myoblasts (SKMs) have been resoundingly negative, and the bone marrow-derived-cell experience leaves much to be desired. A number of lessons arise from the large-scale bone marrow-derived-cell trials: (i) efficacy has been inconsistent and, overall, modest; however, unexpectedly meaningful benefits on clinical end points have been reported; (ii) cardiac engraftment of cells is disappointingly low, and delivery methods need to be optimized and combined with strategies to boost retention; (iii) the cardiomyogeni... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221722 Wed, 07 Sep 2011 04:00:00 +0100 5221722 http://www.medworm.com/index.php?rid=5221721&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900889%26dopt%3DAbstract Response to "Pharmacogenetics: Call to Action" Clin Pharmacol Ther. 2011 Sep 7; Authors: Amstutz U, Carleton BC PMID: 21900889 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221721 Wed, 07 Sep 2011 04:00:00 +0100 5221721 http://www.medworm.com/index.php?rid=5221720&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900890%26dopt%3DAbstract Authors: Barginear MF, Jaremko M, Peter I, Yu C, Kasai Y, Kemeny M, Raptis G, Desnick RJ Abstract Tamoxifen (Tam), the major drug for estrogen receptor (ER)-positive breast cancer, is converted to its active metabolites, Z- and Z'-endoxifen and 4-OH-Tam isomers, primarily by cytochrome P450 CYP2D6. In 117 patients taking 20 mg/day of Tam, we determined CYP2D6 genotypes and measured the plasma levels of Tam metabolites. The Z-endoxifen levels increased while Z'-endoxifen levels decreased with increasing metabolizer phenotype activity (MPA) score (P ≤ 0.0004). The dosage in patients with endoxifen <40 nmol/l and/or CYP2D6 MPA scores of 0 was increased to 30 mg/day and their metabolite isomers were monitored for up to 90 days. Of the 24 patients on the increased dose, 90% show... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221720 Wed, 07 Sep 2011 04:00:00 +0100 5221720 http://www.medworm.com/index.php?rid=5221719&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900891%26dopt%3DAbstract Authors: Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB Abstract Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2-3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Im... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221719 Wed, 07 Sep 2011 04:00:00 +0100 5221719 http://www.medworm.com/index.php?rid=5221718&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900892%26dopt%3DAbstract Authors: Kovacic JC, Fuster V Abstract Cardiovascular disease (CVD) has become the most common cause of mortality worldwide. Obesity, insufficient physical exercise, diabetes, and advancing age are major risk factors for developing cardiovascular disease that are currently increasing in prevalence. Nevertheless, significant progress has recently been made in the treatment of complex cardiovascular and coronary artery disease (CAD), with pharmacological management set to assume an increasingly important role. Other timely factors, such as the development of the polypill and high-level medical and political interest in advancing cardiovascular health, are driving forces that may help to make inroads into the global cardiovascular disease burden. In this article, we critically review ... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5221718 Wed, 07 Sep 2011 04:00:00 +0100 5221718 http://www.medworm.com/index.php?rid=5160426&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862959%26dopt%3DAbstract Authors: PMID: 21862959 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160426 Sat, 27 Aug 2011 06:59:00 +0100 5160426 http://www.medworm.com/index.php?rid=5160425&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862960%26dopt%3DAbstract Authors: Zahedi P, De Souza R, Piquette-Miller M PMID: 21862960 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160425 Sat, 27 Aug 2011 06:58:56 +0100 5160425 http://www.medworm.com/index.php?rid=5160424&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862961%26dopt%3DAbstract Authors: PMID: 21862961 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160424 Sat, 27 Aug 2011 06:58:52 +0100 5160424 http://www.medworm.com/index.php?rid=5160423&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862962%26dopt%3DAbstract Authors: PMID: 21862962 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160423 Sat, 27 Aug 2011 06:58:47 +0100 5160423 http://www.medworm.com/index.php?rid=5160422&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862963%26dopt%3DAbstract Authors: Paine MF PMID: 21862963 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160422 Sat, 27 Aug 2011 06:58:43 +0100 5160422 http://www.medworm.com/index.php?rid=5160421&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862964%26dopt%3DAbstract Authors: Grant D PMID: 21862964 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160421 Sat, 27 Aug 2011 06:58:39 +0100 5160421 http://www.medworm.com/index.php?rid=5160420&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862965%26dopt%3DAbstract Authors: Dollery C Abstract Clinical pharmacology is an essential discipline in the development of new medicines, but the closely specified requirements of pharmaceutical industry protocols and regulatory reviewers have limited the opportunities for curiosity-driven research. Realization is growing that there is so much that is not known about the mechanisms underlying human disease and the actions of medicines on them that research of a more exploratory kind, namely, investigative clinical pharmacology, is a priority. PMID: 21862965 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160420 Sat, 27 Aug 2011 06:58:34 +0100 5160420 http://www.medworm.com/index.php?rid=5160419&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862966%26dopt%3DAbstract Authors: Keith MP, Gilliland WR Abstract Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid (SUA) of <6 mg/dl, remains the standard of care for the chronic management of gout. New urate-lowering medications are important options; however, these agents should be reserved for patients who do not tolerate or cannot achieve SUA <6 mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol therapy suggests that allopurinol should still be considered first-line ULT for gout. PMID: 21862966 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160419 Sat, 27 Aug 2011 06:58:28 +0100 5160419 http://www.medworm.com/index.php?rid=5160418&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862967%26dopt%3DAbstract Authors: PMID: 21862967 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160418 Sat, 27 Aug 2011 06:58:21 +0100 5160418 http://www.medworm.com/index.php?rid=5160417&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862968%26dopt%3DAbstract Authors: PMID: 21862968 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160417 Sat, 27 Aug 2011 06:58:15 +0100 5160417 http://www.medworm.com/index.php?rid=5160416&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862969%26dopt%3DAbstract Authors: PMID: 21862969 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160416 Sat, 27 Aug 2011 06:58:08 +0100 5160416 http://www.medworm.com/index.php?rid=5160415&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21866096%26dopt%3DAbstract Authors: Ouellet D, Sutherland S, Wang T, Griffini P, Murthy V Abstract The pharmacokinetics (PK), safety, and tolerability of GSK1018921, a glycine transporter 1 (GlyT-1) inhibitor, were assessed in this first-time-in-human (FTIH) study. Single oral doses ranging from 0.5 to 280 mg and placebo were administered to 25 healthy subjects in a five-period, two-cohort, crossover study. GSK1018921 showed dose-proportional PK with a terminal half-life of ~17 h. The subjects reported dizziness with a dose-dependent frequency of 22-88% at doses of 70-280 mg. The time course of the dizziness paralleled the PK of the drug, with peak response at 2 h after the dose, consistent with time to maximum plasma concentration (T(max)). The dizziness was resolved by 10-12 h in all subjects. A Markov-c... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160415 Tue, 23 Aug 2011 23:00:00 +0100 5160415 http://www.medworm.com/index.php?rid=5160414&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21866097%26dopt%3DAbstract Authors: Raake PW, Tscheschner H, Reinkober J, Ritterhoff J, Katus HA, Koch WJ, Most P Abstract Heart failure (HF) is the common end point of cardiac diseases. Despite the optimization of therapeutic strategies and the consequent overall reduction in HF-related mortality, the key underlying intracellular signal transduction abnormalities have not been addressed directly. In this regard, the gaps in modern HF therapy include derangement of β-adrenergic receptor (β-AR) signaling, Ca(2+) disbalances, cardiac myocyte death, diastolic dysfunction, and monogenetic cardiomyopathies. In this review we discuss the potential of gene therapy to fill these gaps and rectify abnormalities in intracellular signaling. We also examine current vector technology and currently available vector-deliv... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160414 Tue, 23 Aug 2011 23:00:00 +0100 5160414 http://www.medworm.com/index.php?rid=5160413&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21866098%26dopt%3DAbstract Authors: Tod M, Goutelle S, Gagnieu MC Abstract We propose a framework to enable quantitative prediction of the impact of CYP2D6 polymorphisms on drug exposure. It relies mostly on in vivo data and uses two characteristic parameters: one for the drug and the other for the genotype. The metric of interest is the ratio of drug area under the curve (AUC) in patients with mutant genotype to the AUC in patients with wild-type genotype. Any combination of alleles, as well as duplications, may be accommodated in the framework. Estimates of the characteristic parameters were obtained by orthogonal regression for 40 drugs and five classes of genotypes, respectively, including poor, intermediate, and ultrarapid metabolizers (PMs, IMs, and UMs). The mean prediction error of AUC ratios was -0.... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160413 Tue, 23 Aug 2011 23:00:00 +0100 5160413 http://www.medworm.com/index.php?rid=5160412&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21866099%26dopt%3DAbstract Authors: Haueis P, Greil W, Huber M, Grohmann R, Kullak-Ublick GA, Russmann S Abstract In order to improve medication safety, more epidemiological data on the prevalence and clinical relevance of drug interactions are required. We developed an interface for mass analysis using the Clinical Decision Support Software (CDSS) MediQ and a multidimensional classification (Zurich Interaction System (ZHIAS)) incorporating the Operational Classification of Drug Interactions (ORCA). These were applied to 359,207 cross-sectional prescriptions from 84,607 psychiatric inpatients collected through the international AMSP program. MediQ issued 2,308 "high" and 71,112 "average" danger interaction alerts. Among these, after ORCA reclassification, there were 151 contraindicated and 4,099 provisionall... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5160412 Tue, 23 Aug 2011 23:00:00 +0100 5160412 http://www.medworm.com/index.php?rid=5114379&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21829131%26dopt%3DAbstract Authors: Yamada A, Maeda K, Ishiguro N, Tsuda Y, Igarashi T, Ebner T, Roth W, Ikushiro S, Sugiyama Y Telmisartan is mainly taken up into the liver by organic anion transporting polypeptide (OATP) 1B3, conjugated with glucuronate, and excreted into the bile. We investigated the relationship between genotypes of metabolizing enzymes and transporters and pharmacokinetics of telmisartan in clinical study. We also checked which enzymes are responsible for telmisartan glucuronidation. PMID: 21829131 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5114379 Thu, 11 Aug 2011 10:46:47 +0100 5114379 http://www.medworm.com/index.php?rid=5142984&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21832990%26dopt%3DAbstract Authors: Maeda K, Ikeda Y, Fujita T, Yoshida K, Azuma Y, Haruyama Y, Yamane N, Kumagai Y, Sugiyama Y Abstract Clearance of atorvastatin occurs through hepatic uptake by organic anion transporting polypeptides (OATPs) and subsequent metabolism by cytochrome P450 (CYP) 3A4. To demonstrate the relative importance of OATPs and CYP3A4 in the hepatic elimination of atorvastatin in vivo, a clinical cassette microdose study was performed. A cocktail consisting of a microdose of atorvastatin along with probe substrates for OATPs (pravastatin) and CYP3A4 (midazolam) was orally administered to eight healthy volunteers. The pharmacokinetics of this cocktail was observed at baseline, after an oral dose of 600 mg rifampicin (an inhibitor of OATPs), and after an intravenous dose of 200 mg itracon... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5142984 Tue, 09 Aug 2011 23:00:00 +0100 5142984 http://www.medworm.com/index.php?rid=5142983&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21832991%26dopt%3DAbstract Authors: Hadri L, Hajjar RJ PMID: 21832991 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5142983 Tue, 09 Aug 2011 23:00:00 +0100 5142983 http://www.medworm.com/index.php?rid=5070342&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772290%26dopt%3DAbstract Authors: PMID: 21772290 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070342 Thu, 28 Jul 2011 02:35:00 +0100 5070342 http://www.medworm.com/index.php?rid=5070338&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772291%26dopt%3DAbstract Authors: Reynolds KS PMID: 21772291 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070338 Thu, 28 Jul 2011 02:34:51 +0100 5070338 http://www.medworm.com/index.php?rid=5070337&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772292%26dopt%3DAbstract Authors: PMID: 21772292 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070337 Thu, 28 Jul 2011 02:34:42 +0100 5070337 http://www.medworm.com/index.php?rid=5070336&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772293%26dopt%3DAbstract Authors: PMID: 21772293 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070336 Thu, 28 Jul 2011 02:34:33 +0100 5070336 http://www.medworm.com/index.php?rid=5070333&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772294%26dopt%3DAbstract Authors: van Gelder T PMID: 21772294 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070333 Thu, 28 Jul 2011 02:34:23 +0100 5070333 http://www.medworm.com/index.php?rid=5070331&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772295%26dopt%3DAbstract Authors: Byrne R, Yost SE, Kaplan B PMID: 21772295 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070331 Thu, 28 Jul 2011 02:34:14 +0100 5070331 http://www.medworm.com/index.php?rid=5070330&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772296%26dopt%3DAbstract Authors: Chapman JR PMID: 21772296 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070330 Thu, 28 Jul 2011 02:34:06 +0100 5070330 http://www.medworm.com/index.php?rid=5070329&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772297%26dopt%3DAbstract Authors: Matas AJ PMID: 21772297 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070329 Thu, 28 Jul 2011 02:33:58 +0100 5070329 http://www.medworm.com/index.php?rid=5070328&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772298%26dopt%3DAbstract Authors: Yost SE, Srinivas T, Kaplan B Racial and ethnic disparities exist throughout the US health-care system, including in the field of solid-organ transplant. There are disparities in access to health care, health outcomes, and access to transplant centers. Addressing this issue requires equity in pretransplant care, increased education and referral throughout the transplant process, and research funds targeted to the study of problems pertinent to transplantation in certain patient populations. PMID: 21772298 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070328 Thu, 28 Jul 2011 02:33:48 +0100 5070328 http://www.medworm.com/index.php?rid=5070327&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772299%26dopt%3DAbstract Authors: Newton TF In this issue, Hysek and colleagues present new data describing the impact of treatment with reboxetine on the effects produced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in human volunteers. They demonstrate that several effects of MDMA are mediated by reboxetine's actions on norepinephrine (NE) transporters, an unexpected finding. Building on earlier work, their new data provide new insights into the pharmacodynamics of MDMA and other monoamine-releasing agents. PMID: 21772299 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070327 Thu, 28 Jul 2011 02:33:38 +0100 5070327 http://www.medworm.com/index.php?rid=5070326&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772300%26dopt%3DAbstract Authors: Gieser G, Harigaya H, Colangelo PM, Burckart G PMID: 21772300 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070326 Thu, 28 Jul 2011 02:33:28 +0100 5070326 http://www.medworm.com/index.php?rid=5070325&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772301%26dopt%3DAbstract Authors: PMID: 21772301 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070325 Thu, 28 Jul 2011 02:33:18 +0100 5070325 http://www.medworm.com/index.php?rid=5070324&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21772302%26dopt%3DAbstract Authors: PMID: 21772302 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070324 Thu, 28 Jul 2011 02:33:06 +0100 5070324 http://www.medworm.com/index.php?rid=5070319&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775982%26dopt%3DAbstract Authors: Gassmann-Mayer C, Jiang K, McSorley P, Arani R, Dubrava S, Suryawanshi S, Webb DM, Nilsson M In the past two decades, the potential association between the risk of suicidal ideation and behavior and the clinical use of pharmaceutical products has been debated among industry, regulators, and academia. A better understanding of the possible effects-favorable, unfavorable, or neutral-of pharmaceuticals on the risk of suicidal ideation and behavior may be required, especially for trials typically designed for other primary objectives. Here, a cross-industry statistical team provides recommendations that address the assessment, statistical analysis, interpretation, and utility of suicide-related data in pharmaceutical clinical trials. These recommendations are to evaluate suicidal ... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070319 Tue, 19 Jul 2011 23:00:00 +0100 5070319 http://www.medworm.com/index.php?rid=5070318&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775983%26dopt%3DAbstract Authors: Clarke SJ, Chua W, Moore M, Kao S, Phan V, Tan C, Charles K, McMillan DC PMID: 21775983 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070318 Tue, 19 Jul 2011 23:00:00 +0100 5070318 http://www.medworm.com/index.php?rid=5070317&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775984%26dopt%3DAbstract Authors: Amidon KS, Langguth P, Lennernäs H, Yu L, Amidon GL PMID: 21775984 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070317 Tue, 19 Jul 2011 23:00:00 +0100 5070317 http://www.medworm.com/index.php?rid=5070345&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21753748%26dopt%3DAbstract Authors: Puccetti L, Scarpini F, Cappellone R, Auteri A PMID: 21753748 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070345 Tue, 12 Jul 2011 23:00:00 +0100 5070345 http://www.medworm.com/index.php?rid=5070344&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21753749%26dopt%3DAbstract Authors: de Jonge H, de Loor H, Verbeke K, Vanrenterghem Y, Kuypers DR In vitro studies have identified cyclosporine and tacrolimus as CYP3A inhibitors. In the current study in renal allograft recipients, we used intravenously and orally administered midazolam as a drug probe to assess whether the study drugs at doses that are generally used in clinical practice have differential effects on in vivo hepatic and first-pass CYP3A activities. Systemic and apparent oral midazolam clearance were 24% (269 ± 73 vs. 354 ± 102 ml/min, P = 0.022) and 31% (479 ± 190 vs. 688 ± 265 ml/min, P = 0.013), respectively, lower in cyclosporine-treated patients (n = 20) than in matched tacrolimus-treated patients (n = 20). The latter displayed midazolam clearances similar to those in two larger cohort... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5070344 Tue, 12 Jul 2011 23:00:00 +0100 5070344 http://www.medworm.com/index.php?rid=5019575&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21734654%26dopt%3DAbstract Authors: Raghavaiah S, Stegall MD PMID: 21734654 [PubMed - as supplied by publisher] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=5019575 Tue, 05 Jul 2011 23:00:00 +0100 5019575 http://www.medworm.com/index.php?rid=4972579&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691264%26dopt%3DAbstract Authors: PMID: 21691264 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972579 Tue, 28 Jun 2011 05:00:41 +0100 4972579 http://www.medworm.com/index.php?rid=4972578&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691265%26dopt%3DAbstract Authors: Vincent J PMID: 21691265 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972578 Tue, 28 Jun 2011 05:00:37 +0100 4972578 http://www.medworm.com/index.php?rid=4972577&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691266%26dopt%3DAbstract Authors: Waldman SA, Hohl RJ, Kearns GL, Swan SJ, Terzic A PMID: 21691266 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972577 Tue, 28 Jun 2011 05:00:34 +0100 4972577 http://www.medworm.com/index.php?rid=4972576&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691267%26dopt%3DAbstract Authors: PMID: 21691267 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972576 Tue, 28 Jun 2011 05:00:30 +0100 4972576 http://www.medworm.com/index.php?rid=4972575&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691268%26dopt%3DAbstract Authors: PMID: 21691268 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972575 Tue, 28 Jun 2011 05:00:27 +0100 4972575 http://www.medworm.com/index.php?rid=4972574&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691269%26dopt%3DAbstract Authors: Prabhakaran D, Reddy KS PMID: 21691269 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972574 Tue, 28 Jun 2011 05:00:23 +0100 4972574 http://www.medworm.com/index.php?rid=4972573&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691270%26dopt%3DAbstract Obesity and the "obesity paradox" in cardiovascular diseases. Clin Pharmacol Ther. 2011 Jul;90(1):23-5 Authors: Lavie CJ, Milani RV, Ventura HO Obesity adversely affects most cardiovascular (CV) risk factors and is strongly associated, probably as an independent risk factor, with most CV diseases. However, substantial evidence points to the existence of an "obesity paradox," in that overweight and obese patients with established CV diseases typically have a better prognosis than leaner patients with the same CV disease. Despite this paradox, we believe that the "weight" of evidence still supports efforts at purposeful weight loss in both primary and secondary CV prevention. PMID: 21691270 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972573 Tue, 28 Jun 2011 05:00:19 +0100 4972573 http://www.medworm.com/index.php?rid=4972572&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691271%26dopt%3DAbstract Authors: Haga SB, Burke W Pharmacogenomic tests offer a promising strategy to improve the safety and efficacy of drug treatment. Compelling examples, such as HLA-B*5701 testing to identify patients at risk for abacavir-associated hypersensitivity, are already changing clinical care. However, the level of evidence required to establish clinical utility is often the subject of debate. Determining the most efficient and effective pathway to benefit for a given test is therefore both a practical and an ethical concern. PMID: 21691271 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972572 Tue, 28 Jun 2011 05:00:15 +0100 4972572 http://www.medworm.com/index.php?rid=4972571&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691272%26dopt%3DAbstract This article provides insights into the importance and challenges of using such evidence through the case study of nonfatal myocardial infarction (MI) and nonfatal bleeding with prasugrel. PMID: 21691272 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972571 Tue, 28 Jun 2011 05:00:11 +0100 4972571 http://www.medworm.com/index.php?rid=4972570&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691273%26dopt%3DAbstract Authors: Tominaga T, Asahina Y, Uyama Y, Kondo T Development of innovative drugs has recently become more difficult. The case of rosiglitazone shows the extreme difficulty of making the regulatory decision that will best balance the benefits and risks of a drug. There is a high expectation that regulatory science (RS) can improve the situation. However, without user understanding of its basic characteristics, RS will not deliver what is expected. PMID: 21691273 [PubMed - in process] (Source: Clinical Pharmacology and Therapeutics) Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972570 Tue, 28 Jun 2011 05:00:07 +0100 4972570 http://www.medworm.com/index.php?rid=4972581&cid=s_34412_13_f&fid=34412&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21677639%26dopt%3DAbstract This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans. ... Clinical Pharmacology and Therapeutics journals http://www.medworm.com/rss/comments.php?id=4972581 Tue, 14 Jun 2011 23:00:00 +0100 4972581