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583 records returned

Desirudin Dosing and Monitoring in Moderate Renal Impairment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to evaluate appropriate desirudin dosing in moderate renal impairment and the effect of desirudin on aPTT in moderate renal impairment. Desirudin plasma concentration and aPTT data were extracted from 6 studies. Participants with normal renal function or moderate renal impairment (creatinine clearance [ClCr] 31-60 mL/min) were included. Pharmacokinetic and Monte Carlo simulations were done. After administration of desirudin 15 mg every 12 hours subcutaneously (SC) to steady state, peak desirudin concentrations were 35 and 47 nmol/L in the normal and moderate renal function groups, respective...
Source: The Journal of Clinical Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Nafziger AN, Bertino JS Tags: J Clin Pharmacol Source Type: journals

Pharmacokinetics of Loxapine Following Inhalation of a Thermally Generated Aerosol in Healthy Volunteers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this randomized, double-blind, placebo-controlled, dose escalation study was to determine the pharmacokinetic characteristics, safety, and tolerability of single doses of inhaled loxapine aerosol in healthy volunteers. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Fifty participants were randomized to receive 0.625, 1.25, 2.5, 5.0, or 10 mg of loxapine aerosol or placebo. Following inhalation, the tmax median (25%, 75%) was 2 (1, 3) minutes. The loxapine AUCinfinity was dose proportional across all...
Source: The Journal of Clinical Pharmacology - November 13, 2009 Category: Drugs & Pharmacology Authors: Spyker DA, Munzar P, Cassella JV Tags: J Clin Pharmacol Source Type: journals

Antihypertensive Drug Adherence Among 6408 Chinese Patients on Angiotensin-Converting Enzyme Inhibitors in Hong Kong: A Cohort Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study evaluated the factors associated with adherence with angiotensin-converting enzyme inhibitors (ACEIs), an increasingly common antihypertensive drug of choice. The authors included all adult patients who were prescribed an ACEI and paid at least 2 consecutive visits to any primary care clinics of one large territory of Hong Kong from January 2004 to June 2007. The determinants of good adherence to ACEI, as defined by a medication possession ratio >/=80%, were evaluated by multivariate regression analysis. From 6408 eligible patients, 88.0% were adherent. Patients attending family medicine specialist clinics (a...
Source: The Journal of Clinical Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Wong MC, Jiang JY, Griffiths SM Tags: J Clin Pharmacol Source Type: journals

Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1-compartment model. Final model estimates of clearance, volume of...
Source: The Journal of Clinical Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Vezina HE, Balfour HH, Weller DR, Anderson BJ, Brundage R Tags: J Clin Pharmacol Source Type: journals

Estimating the Contribution of Genes to Variation in Renal Drug Clearance by Active Secretion Using Multiple Data From Clinical Phase I Studies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19897765 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - November 6, 2009 Category: Drugs & Pharmacology Authors: Fujita T, Kumagai Y, Nakahara I, Ohtani Y, Majima M Tags: J Clin Pharmacol Source Type: journals

Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An exposure-response (E-R) analysis using linear mixed effects modeling was conducted on data from a thorough QTc trial for asenapine in 148 patients with schizophrenia. In a parallel design, patients received asenapine 5 mg twice daily (BID) for 10 days (10d) followed by 10 mg BID (6d), asenapine 15 mg BID (10d) followed by 20 mg BID (6d), quetiapine 375 mg BID (for assay sensitivity; 16d) or placebo (16d). Triplicate 12-lead electrocardiograms and concentration measurements were obtained on day -1 (baseline), 1, 10, and 16 at 8 scheduled times on each day. At mean C(max) for all asenapine doses, the E-R model predict...
Source: The Journal of Clinical Pharmacology - October 24, 2009 Category: Drugs & Pharmacology Authors: Chapel S, Hutmacher MM, Haig G, Bockbrader H, de Greef R, Preskorn SH, Lalonde RL Tags: J Clin Pharmacol Source Type: journals

Quantitative analysis of T-wave morphology increases confidence in drug-induced cardiac repolarization abnormalities: evidence from the investigational IKr inhibitor Lu 35-138.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigates repolarization changes induced by a new candidate drug to determine whether a composite electrocardiographic (ECG) measure of T-wave morphology could be used as a reliable marker to support the evidence of abnormal repolarization, which is indicated by QT interval prolongation. Seventy-nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an I(Kr)-blocking antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used to determine a combined measure of rep...
Source: The Journal of Clinical Pharmacology - October 24, 2009 Category: Drugs & Pharmacology Authors: Graff C, Matz J, Christensen EB, Andersen MP, Kanters JK, Toft E, Pehrson S, Hardahl TB, Nielsen J, Struijk JJ Tags: J Clin Pharmacol Source Type: journals

Population Pharmacokinetics of Perphenazine in Schizophrenia Patients From CATIE: Impact of Race and Smoking.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The goal of the study was to characterize population pharmacokinetics (PPK) for perphenazine in patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Patients (n = 156) received 8 to 32 mg of perphenazine daily for 14 to 600 days for a total of 421 plasma concentrations measurements. Nonlinear mixed-effects modeling was used to determine PPK characteristics of perphenazine. One- and 2-compartment models with various random effect implementations and mixture distributions were evaluated. Objective function values and goodness-of-fit plots were used as model selection c...
Source: The Journal of Clinical Pharmacology - October 19, 2009 Category: Drugs & Pharmacology Authors: Jin Y, Pollock BG, Coley K, Miller D, Marder SR, Florian J, Schneider L, Lieberman J, Kirshner M, Bies RR Tags: J Clin Pharmacol Source Type: journals

Effect of Age, Weight, and CYP2C19 Genotype on Escitalopram Exposure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study was to characterize escitalopram population pharmacokinetics (PK) in patients treated for major depression in a cross-national, US-Italian clinical trial. Data from the 2 sites participating in this trial, conducted at Pittsburgh (United States) and Pisa (Italy), were used. Patients received 5, 10, 15, or 20 mg of escitalopram daily for a minimum of 32 weeks. Nonlinear mixed effects modeling was used to model the PK characteristics of escitalopram. One- and 2-compartment models with various random effect implementations were evaluated during model development. Objective function values and goo...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Jin Y, Pollock BG, Frank E, Cassano GB, Rucci P, Müller DJ, Kennedy JL, Forgione RN, Kirshner M, Kepple G, Fagiolini A, Kupfer DJ, Bies RR Tags: J Clin Pharmacol Source Type: journals

Systemic Bioavailability of Topical Diclofenac Sodium Gel 1% Versus Oral Diclofenac Sodium in Healthy Volunteers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50-mg tablets. In a randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7-day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily. Thirty-nine participants completed all 3 regimens. Systemic exposure was ...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Kienzler JL, Gold M, Nollevaux F Tags: J Clin Pharmacol Source Type: journals

Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferonbased therapy were ...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Berman J, Liu QY, Doo E, Fried MW Tags: J Clin Pharmacol Source Type: journals

Itraconazole and Rifampin Alter Significantly the Disposition and Antihistamine Effect of Ebastine and Its Metabolites in Healthy Participants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study was performed to elucidate the effects of itraconazole and rifampin on the pharmacokinetics and pharmacodynamics of ebastine, a nonsedative H1 receptor antagonist. In a 3-way crossover sequential design with 2-week washouts, 10 healthy participants were pretreated with itraconazole for 6 days, rifampin for 10 days, or neither. After oral administration of 20 mg ebastine, blood and urine samples were collected for 72 and 24 hours, respectively, and histamine-induced wheal and flare reactions were measured to assess the antihistamine response for 12 hours. Itraconazole pretreatment decreased the oral cl...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Shon JH, Yeo CW, Liu KH, Lee SS, Cha IJ, Shin JG Tags: J Clin Pharmacol Source Type: journals

Specific and Pronounced Impacts of Lisinopril and Lisinopril Plus Simvastatin on Erythrocyte Antioxidant Enzymes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehyd...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Kaminsky Y, Suslikov A, Kosenko E Tags: J Clin Pharmacol Source Type: journals

No Pharmacokinetic Interaction Between Lacosamide and Carbamazepine in Healthy Volunteers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lacosamide is a new antiepileptic drug for adjunctive treatment of adult partial-onset seizures. Two open-label, multiple-dose clinical trials were conducted to evaluate the potential for pharmacokinetic interaction between lacos amide and carbamazepine. The influence of carbamazepine on lacosamide pharmacokinetics (trial A) and lacosamide on carbamazepine pharmacokinetics (trial B) was investi gated in 19 (trial A) and 18 (trial B) healthy male partici pants. Trial A participants received lacosamide 200 mg bid alone and with carbamazepine 200 mg bid. Trial B partici pants received carbamazepine 200 mg bid alone and wi...
Source: The Journal of Clinical Pharmacology - October 18, 2009 Category: Drugs & Pharmacology Authors: Cawello W, Nickel B, Eggert-Formella A Tags: J Clin Pharmacol Source Type: journals

Clinical Pharmacokinetics and Exposure-Toxicity Relationship of a Folate-Vinca Alkaloid Conjugate EC145 in Cancer Patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, EC145 is rapidly distributed and eliminated in cancer patients. BSA is a statistically significant covariate on EC145 clearance, but its clinical relevance remains to be defined. EC145-induced constipation occurs at a higher frequency in the patients with lower EC145 clearance, where the drug exposure tends to be higher. PMID: 19837906 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - October 15, 2009 Category: Drugs & Pharmacology Authors: Li J, Sausville EA, Klein PJ, Morgenstern D, Leamon CP, Messmann RA, Lorusso P Tags: J Clin Pharmacol Source Type: journals

Interspecies Scaling of Therapeutic Monoclonal Antibodies: Initial Look.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors evaluated interspecies scaling for the prediction of human clearance of 18 therapeutic monoclonal antibodies (mAbs). Human and monkey/chimpanzee data of 14 mAbs were classified based on the targeted antigens (soluble or membrane bound). Simple allometry and/or a time-invariant method (elementary Dedrick plot) were performed. Results indicate that human clearance might be accurately predicted from monkey data for mAbs targeting soluble receptors or membrane-bound receptors with limited tissue distribution using simplified allometry. The optimal exponents were estimated to be 0.85 or If nonlinearity is antici...
Source: The Journal of Clinical Pharmacology - October 15, 2009 Category: Drugs & Pharmacology Authors: Ling J, Zhou H, Jiao Q, Davis HM Tags: J Clin Pharmacol Source Type: journals

Influence of Development, HIV Infection, and Antiretroviral Therapies on the Gene Expression Profiles of ABC Transporters in Human Lymphocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns. PMID: 19837908 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - October 15, 2009 Category: Drugs & Pharmacology Authors: Giraud C, Manceau S, Declèves X, Goffinet F, Morini JP, Chappuy H, Batteux F, Chouzenoux S, Yousif S, Scherrmann JM, Blanche S, Tréluyer JM Tags: J Clin Pharmacol Source Type: journals

Absence of Effect of Telbivudine on Cardiac Repolarization: Results of a Thorough QT/QTc Study in Healthy Participants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study therefore met the criteria for a negative thorough QT study. Telbivudine had no adverse effect on cardiac repolarization in healthy participants, even at supratherapeutic exposure, suggesting a broad safety margin. PMID: 19833860 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - October 14, 2009 Category: Drugs & Pharmacology Authors: Poordad F, Zeldin G, Harris SI, Ke J, Xu L, Mayers D, Zhou XJ Tags: J Clin Pharmacol Source Type: journals

Laropiprant in Combination With Extended-Release Niacin Does Not Alter Urine 11-Dehydrothromboxane B2, a Marker of In Vivo Platelet Function, in Healthy, Hypercholesterolemic, and Diabetic Subjects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Laropiprant, an antagonist of the PGD2 receptor, DP1, is effective in reducing the flushing symptoms associated with extended-release (ER) niacin and thereby improves the tolerability of niacin therapy for dyslipidemia. Because PGD2 has been reported to inhibit platelet aggregation in vitro, it has been speculated that antagonism of DP1 may enhance platelet reactivity. Three clinical studies evaluated the potential effect of laropiprant, with or without coadministration of ER niacin, on in vivo platelet function in healthy subjects and hypercholesterolemic or diabetic subjects by measuring urinary levels of 11-dehydrot...
Source: The Journal of Clinical Pharmacology - October 14, 2009 Category: Drugs & Pharmacology Authors: Lauring B, Dishy V, Luo WL, Laterza O, Patterson J, Cote J, Chao A, Larson P, Gutierrez M, Wagner JA, Lai E Tags: J Clin Pharmacol Source Type: journals

Lack of Electrocardiographic Effect of Dexlansoprazole MR, a Novel Modified-Release Formulation of the Proton Pump Inhibitor Dexlansoprazole, in Healthy Participants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The effect of the proton pump inhibitor dexlansoprazole, an enantiomer of lansoprazole, on QT intervals was assessed after oral administration of a modifiedrelease formulation of dexlansoprazole (dexlansoprazole MR). In this randomized, positivecomparator, placebocontrolled, 4period crossover study, 40 healthy participants received single doses of dexlansoprazole MR 90 mg, dexlansoprazole MR 300 mg, moxifloxacin 400 mg, and placebo separated by 5day washout intervals. Twentyfourhour electrocardiograms were obtained at baseline and during each dosing period. The number and percentage of participants experiencing an incr...
Source: The Journal of Clinical Pharmacology - October 12, 2009 Category: Drugs & Pharmacology Authors: Vakily M, Wu J, Atkinson SN Tags: J Clin Pharmacol Source Type: journals

Pleiotropic Effects of Atorvastatin on Monocytes in Atherosclerotic Patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to investigate the gene expression signature of monocyte/macrophages and the pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients. Forty patients with coronary heart diseases were randomly assigned to double-blind therapy with either 20 or 80 mg per day of atorvastatin. Follow-up visits occurred at weeks 6 and 12, including complete chemistry and lipid analyses and quantification of 14 target genes in monocytes. After 12 weeks of therapy, both groups gained beneficial alterations in lipid profiles. Both groups experienced significant reductions in gene expression of l...
Source: The Journal of Clinical Pharmacology - October 5, 2009 Category: Drugs & Pharmacology Authors: Wang ZH, Liu XL, Zhong M, Zhang LP, Shang YY, Hu XY, Li L, Zhang Y, Deng JT, Zhang W Tags: J Clin Pharmacol Source Type: journals

A Phase I Study to Characterize the Safety, Tolerability, and Pharmacokinetics of Topotecan at 4 mg/m2 Administered Weekly as a 30-Minute Intravenous Infusion in Patients With Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Topotecan pharmacokinetics at higher infusion rates (4 mg/m(2) over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4-mg/m(2) topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, V, C, t, t1/2, AUC0-t, and AUC0-infinity. Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, Vss value of 101 L, and...
Source: The Journal of Clinical Pharmacology - October 5, 2009 Category: Drugs & Pharmacology Authors: Curtis KK, Hartney JT, Jewell RC, Park JW, Lebowitz PF, Griffin PP, Borad MJ, Fitch TR, Northfelt DW Tags: J Clin Pharmacol Source Type: journals

Effect of Thyroid Hormone on the Activity of CYP3A Enzyme in Humans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Thyroid hormones have been shown to reduce the activity and expression of cytochrome P450 (CYP) 3A4 in vitro. The influence of thyroid hormone on drug action via a CYP3A-dependent pathway has not been elucidated in humans. This is the first report showing the effect of thy roid hormone on CYP3A enzyme activity in humans. Ten healthy volunteers participate in this open-label study, in which the pharmacokinetics of midazolam and the urinary ratios of 6 beta-hydroxycortisol/free cortisol before and after 2 weeks of oral administration of triiodothyronine were compared. Triiodothyronine administration significantly reduced...
Source: The Journal of Clinical Pharmacology - October 5, 2009 Category: Drugs & Pharmacology Authors: Takahashi N, Inui N, Morita H, Takeuchi K, Uchida S, Watanabe H, Nakamura H Tags: J Clin Pharmacol Source Type: journals

The Effects of a Short Course of Antibiotics on Alvimopan and Metabolite Pharmacokinetics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to characterize the pharmacokinetics of alvimopan and metabolite before, during, and after administration of a short course of antibiotics in healthy adult participants. Simulations were conducted to determine the feasibility for this study. An open-label, sequential drug interaction study was conducted in 45 participants who received twice-daily dosing of alvimopan with and without ciprofloxacin. Metabolite concentrations were reduced by 99.2% (90% confidence interval: 98.8-99.5) in the presence of ciprofloxacin. The interaction occurred rapidly, and recovery was slow. The interaction may b...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Schmith VD, Johnson BM, Vasist LS, Kelleher DL, Hewens DA, Young MA, Ameen V, Dukes GE Tags: J Clin Pharmacol Source Type: journals

Pharmacokinetics of Trans-resveratrol Following Repeated Administration in Healthy Elderly and Young Subjects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19797536 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Nunes T, Almeida L, Rocha JF, Falcão A, Fernandes-Lopes C, Loureiro AI, Wright L, Vaz-da-Silva M, Soares-da-Silva P Tags: J Clin Pharmacol Source Type: journals

A Systematic Review and Empirical Analysis of the Relation Between Dose and Duration of Drug Action.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There is a log-linear relation between the dose and duration of action of drugs with single-compartment pharmacokinetics and direct, reversible mechanisms of action. However, it has been suggested that this relation does not extend to drugs whose metabolites are active or slowly eliminated, drugs with saturable kinetics, and drugs with hit-and-run effects. The purpose of this study is to test this hypothesis and to quantify the relationship by way of a systematic review coupled to an empirical analysis. All issues of 4 clinical pharmacology journals from 1980 to 2005 are hand-searched for articles that present pharmaco...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Hughes DA, Aronson JK Tags: J Clin Pharmacol Source Type: journals

Exposure to Hydroxyurea During Pregnancy in Sickle-{beta} Thalassemia: A Report of 2 Cases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hydroxyurea, used in the treatment of sickle cell anemia, is a teratogenic drug. However, the potential benefits of the drug far outweigh its risks when the fetus of the patient on hydroxyurea therapy gets exposed to the drug in an unplanned pregnancy. The authors present 2 clinically severe cases of patients with sickle-beta thalas semia who became pregnant while on hydroxyurea therapy and delivered healthy babies. Hydroxyurea was stopped after the confirmation of the pregnancy and was restarted after the termination of breastfeeding. Seven cases of fetal exposure to hydroxyurea have been reported among sickle cell an...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Italia KY, Jijina FF, S C, Nadkarni AH, Sawant P, Ghosh K, Colah RB Tags: J Clin Pharmacol Source Type: journals

Multiple Doses of Sitagliptin, a Selective DPP-4 Inhibitor, Do Not Meaningfully Alter Pharmacokinetics and Pharmacodynamics of Warfarin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve participants received treatments A and B separated by >7-day washout: treatment A involved coadministration of sitagliptin 200 mg/d for 11 days (days 1-11) and warfarin 30 mg on day 5, and treatment B involved warfarin 30 mg alone on day 1. R(+) warfarin, S(-) warfarin, and international normalized ratio (INR...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Wright DH, Herman GA, Maes A, Liu Q, Johnson-Levonas AO, Wagner JA Tags: J Clin Pharmacol Source Type: journals

Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study sought to determine whether the presence of in vitro anticholinergic activity (AA) among different drugs is associated with reporting of neuropsychiatric adverse events (NPAEs) and whether age affects this relationship. Retrospective case/noncase analyses using Australia's spontaneous Adverse Drug Reaction System (ADRS) database containing 150 475 reports determined crude and adjusted reporting odds ratios (RORs) for NPAEs for 23 drugs with various reported in vitro AA. Covariates were age (treated as a dichotomous variable [>/=65 years]), gender, and concomitant use of antipsychotics, benzodiazepines, tricyc...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Nishtala PS, Fois RA, McLachlan AJ, Bell JS, Kelly PJ, Chen TF Tags: J Clin Pharmacol Source Type: journals

Quantitative structure-property relationships modeling to predict in vitro and in vivo binding of drugs to the bile sequestrant, colesevelam (welchol).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Quantitative structure-property relationship (QSPR) models were developed to correlate physicochemical properties of structurally unrelated drugs with extent of in vitro binding to colesevelam, and predicted values were compared with drug exposure changes in vivo following coadministration. The binding of 17 drugs to colesevelam was determined by an in vitro dissolution drug-binding assay. Data from several clinical studies in healthy volunteers to support administration of colesevelam in diabetic patients were also collected along with existing in vivo literature data and compared with in vitro results. Steric, electr...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Walker JR, Brown K, Rohatagi S, Bathala MS, Xu C, Wickremasingha PK, Salazar DE, Mager DE Tags: J Clin Pharmacol Source Type: journals

Bioavailability of mycophenolate mofetil and enteric-coated mycophenolate sodium is differentially affected by pantoprazole in healthy volunteers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The influence of pantoprazole 40 mg twice daily on the bioavailability of a single dose of mycophenolate mofetil 1000 mg or enteric-coated mycophenolate sodium is investigated in healthy volunteers. The plasma concentrations of mycophenolic acid and of the inactive metabolite mycophenolic acid glucuronide are measured by high-performance liquid chromatography. The pharmacokinetic parameters following sole administration are similar for mycophenolate mofetil and enteric-coated mycophenolate sodium except for the time to peak concentration, which is longer in the enteric-coated mycophenolate sodium group. Concomitant tre...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Rupprecht K, Schmidt C, Raspé A, Schweda F, Shipkova M, Fischer W, Bucher M, Kees F, Faerber L Tags: J Clin Pharmacol Source Type: journals

Examination of the effect of increasing doses of etoricoxib on oral methotrexate pharmacokinetics in patients with rheumatoid arthritis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors designed 2 randomized controlled studies to examine the effects of etoricoxib 60 to 120 mg daily on methotrexate pharmacokinetics in 50 rheumatoid arthritis (RA) patients on stable doses of methotrexate (7.5-20 mg). Patients received oral methotrexate at baseline and on days 7 and 14. In study 1, patients received etoricoxib 60 mg (days 1-7) and then 120 mg (days 8-14); in study 2, patients received etoricoxib 90 mg (days 1-7) and then 120 mg (days 8-14). For study 1, the AUC(0-infinity) geometric mean ratio (GMR) (90% confidence interval [CI]) for day 7 versus baseline was 1.01 (0.91, 1.12) for etoricoxib ...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Schwartz JI, Agrawal NG, Wong PH, Miller J, Bachmann K, Marbury T, Hoelscher D, Cavanaugh PF, Gottesdiener K Tags: J Clin Pharmacol Source Type: journals

Pharmacokinetics, Safety, and Tolerability of Phentermine in Healthy Participants Receiving Taranabant, a Novel Cannabinoid-1 Receptor (CB1R) Inverse Agonist.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study assessed the potential pharmacokinetic interaction and safety/tolerability of taranabant and phentermine coadministration. This was a randomized, double-blind, 3-panel, fixed-sequence study in healthy participants. Panels A, B, and C evaluated the safety/tolerability of phentermine 15 mg coadministered with taranabant 0.5, 1, and 2 mg for 7 days (panel A) and 28 days (panels B and C). In panels A and C, phentermine 15 mg was administered both with (7 days, panel A; 28 days, panel C) and without (7 days) taranabant 0.5 mg or 2 mg to evaluate pharmacokinetics. The primary endpoint was phentermine AUC(0-24 h) in pa...
Source: The Journal of Clinical Pharmacology - September 30, 2009 Category: Drugs & Pharmacology Authors: Addy C, Jumes P, Rosko K, Li S, Li H, Maes A, Johnson-Levonas AO, Chodakewitz J, Stoch SA, Wagner JA Tags: J Clin Pharmacol Source Type: journals

Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty-two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15-microg/kg bolus followed by a 2-microg/kg/ min infusion or a 30-microg/kg bolus followed by a 4-microg/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters. Administration of an intravenous bolus followed...
Source: The Journal of Clinical Pharmacology - September 23, 2009 Category: Drugs & Pharmacology Authors: Akers WS, Oh JJ, Oestreich JH, Ferraris S, Wethington M, Steinhubl SR Tags: J Clin Pharmacol Source Type: journals

Pharmacokinetics and Safety of Sunitinib Malate in Subjects With Impaired Renal Function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This phase I, open-label, single-dose study evaluates the effects of severe renal impairment and end-stage renal disease (ESRD) requiring hemodialysis on the pharmacokinetics, safety, and tolerability of sunitinib and its primary active metabolite, SU12662. Subjects with normal renal function (creatinine clearance > 80 mL/min), severe renal impairment (creatinine clearance < 30 mL/min), and ESRD requiring hemodialysis receive a single dose of sunitinib 50 mg. Serial blood samples are collected for quantification of plasma concentrations using a validated liquid chromatography with tandem mass spectrometry assay. ...
Source: The Journal of Clinical Pharmacology - September 23, 2009 Category: Drugs & Pharmacology Authors: Khosravan R, Toh M, Garrett M, La Fargue J, Ni G, Marbury TC, Swan SK, Lunde NM, Bello CL Tags: J Clin Pharmacol Source Type: journals

Quantitative Population Pharmacokinetic Analysis of Pravastatin Using an Enterohepatic Circulation Model Combined With Pharmacogenomic Information on SLCO1B1 and ABCC2 Polymorphisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aims of this study were to develop a population pharmacokinetic (PPK) model for pravastatin pharmacokinetics with regard to enterohepatic circulation (EHC) and to evaluate effects of polymorphisms in SLCO1B1 and ABCC2 on the pharmacokinetic (PK) profile of pravastatin quantitatively. A total of 636 blood samples from 57 healthy male volunteers were used. The PPK analysis was carried out using nonlinear mixed effect modeling (NONMEM) and validated by a bootstrap analysis. The PK profile of pravastatin was best described by a model of EHC with Erlang's distribution. A covariate analysis revealed that SLCO1B1*15 signi...
Source: The Journal of Clinical Pharmacology - September 22, 2009 Category: Drugs & Pharmacology Authors: Ide T, Sasaki T, Maeda K, Higuchi S, Sugiyama Y, Ieiri I Tags: J Clin Pharmacol Source Type: journals

Microdose Pharmacokinetics of IDX899 and IDX989, Candidate HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors, Following Oral and Intravenous Administration in Healthy Male Subjects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IDX899 and IDX989 are new non-nucleoside reversetranscriptase inhibitors (NNRTIs) that exhibit potent inhibition of HIV-1 replication, including NNRTI-resistant mutants. This microdose study investigates the pharmacokinetics and determined oral bioavailability. For each compound, 4 healthy male subjects are randomized to receive via a crossover design a single 100-microg oral and intravenous dose together with 100 nCi of [(14)C]-labeled drug. Plasma and urine samples are obtained over a period of 168 hours postdose and analyzed for total, unchanged drug and major metabolites using an accelerator mass spectrometry metho...
Source: The Journal of Clinical Pharmacology - September 22, 2009 Category: Drugs & Pharmacology Authors: Zhou XJ, Garner RC, Nicholson S, Kissling CJ, Mayers D Tags: J Clin Pharmacol Source Type: journals

Valproic Acid Plasma Concentration Decreases in a Dose-Independent Manner Following Administration of Meropenem: A Retrospective Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, the interaction between meropenem and VPA causes a significant decrease in VPA plasma concentration, apparently within 24 hours. As the therapeutic effects of VPA are plasma concentration dependent, the data suggest that these drugs should not be administered concomitantly. PMID: 19773524 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - September 21, 2009 Category: Drugs & Pharmacology Authors: Haroutiunian S, Ratz Y, Rabinovich B, Adam M, Hoffman A Tags: J Clin Pharmacol Source Type: journals

Population Pharmacokinetics of Teduglutide Following Repeated Subcutanenous Administrations in Healthy Participants and in Patients With Short Bowel Syndrome and Crohn's Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Teduglutide is a GLP-2 analog currently evaluated for the treatment of short bowel syndrome, Crohn's disease, and other gastrointestinal disorders. The population pharmacokinetics (PK) of teduglutide were assessed following daily subcutaneous (SC) administrations of 2.5 to 80 mg doses in a total of 256 patients. A 1-compartment model with a site-specific rate constant of absorption in the abdomen, arm, and thigh was used to assess the PK of teduglutide. Apparent clearance (CL/F) of teduglutide in male participants was approximately 18% higher than that observed in female participants (12.4 vs 10.5 L/h, respectively). B...
Source: The Journal of Clinical Pharmacology - September 21, 2009 Category: Drugs & Pharmacology Authors: Marier JF, Mouksassi MS, Gosselin NH, Beliveau M, Cyran J, Wallens J Tags: J Clin Pharmacol Source Type: journals

Effect of Telithromycin on the Pharmacokinetics and Pharmacodynamics of Oral Oxycodone.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, telithromycin clearly reduces the N-demethylation of oxycodone to noroxycodone by inhibiting the CYP450 3A4 enzyme. The use of telithromycin in patients receiving multiple doses of oxycodone for pain relief may increase the risk of opioid adverse effects. Reduction of oxycodone dose by 25% to 50% followed by readjustment according to the clinical response might be appropriate. PMID: 19755414 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - September 14, 2009 Category: Drugs & Pharmacology Authors: Grönlund J, Saari T, Hagelberg N, Martikainen IK, Neuvonen PJ, Olkkola KT, Laine K Tags: J Clin Pharmacol Source Type: journals

Acute Hemodynamic Effects of Single-Dose Sildenafil When Added to Established Bosentan Therapy in Patients With Pulmonary Arterial Hypertension: Results of the COMPASS-1 Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigated the acute pharmacodynamic effects of sildenafil in patients with pulmonary arterial hypertension (PAH) and concomitant bosentan treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs. This prospective, open-label, noncomparative, multicenter, phase II study enrolled 45 patients (>/=18 years) with stable PAH (idiopathic, familial, or related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins) and on bosentan treatment for at least 3 months. Patients underwent right heart catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric oxid...
Source: The Journal of Clinical Pharmacology - September 14, 2009 Category: Drugs & Pharmacology Authors: Gruenig E, Michelakis E, Vachiéry JL, Vizza CD, Meyer FJ, Doelberg M, Bach D, Dingemanse J, Galiè N Tags: J Clin Pharmacol Source Type: journals

Absence of QTc Prolongation in a Thorough QT Study With Subcutaneous Liraglutide, a Once-Daily Human GLP-1 Analog for Treatment of Type 2 Diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc i...
Source: The Journal of Clinical Pharmacology - September 7, 2009 Category: Drugs & Pharmacology Authors: Chatterjee DJ, Khutoryansky N, Zdravkovic M, Sprenger CR, Litwin JS Tags: J Clin Pharmacol Source Type: journals

Is a Thorough QTc Study Necessary? The Role of Modeling and Simulation in Evaluating the QTc Prolongation Potential of Drugs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Concentration-QT (C-QT) modeling has been conducted for multiple compounds at various stages of development in different therapeutic areas. Data from available single and multiple ascending-dose (SAD/MAD) studies were pooled to construct population C-QT models, with post hoc predictions of concentration from a pharmacokinetic model. All SAD and MAD studies employed a customized robust QTc assessment with time-matched triplicate electrocardiograms and centralized manual QTc reading. Sources of variability were characterized, and the relationship between covariates and model parameters was explored, with a particular emp...
Source: The Journal of Clinical Pharmacology - September 3, 2009 Category: Drugs & Pharmacology Authors: Rohatagi S, Carrothers TJ, Kuwabara-Wagg J, Khariton T Tags: J Clin Pharmacol Source Type: journals

Hypersensitivity Syndrome Induced by Anticonvulsants: Possible Cross-Reactivity Between Carbamazepine and Lamotrigine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A 14-year-old male presents with erythroderma and fever 44 days after carbamazepine intake. Laboratory exams show eosinophilia and elevated liver enzymes, and thoracic imaging reveals interstitial pneumonitis. All symptoms disappear after carbamazepine withdrawal. A patch test to carbamazepine performed 6 weeks after recovery is positive. About 8 months later, the patient exhibits the same clinical and biological picture 52 days after lamotrigine intake. Lamotrigine is stopped and all symptoms disappear. A patch test to LMG is positive. This case illustrates a possible cross-reactivity between carbamazepine and lamotri...
Source: The Journal of Clinical Pharmacology - August 31, 2009 Category: Drugs & Pharmacology Authors: Aouam K, Ben Romdhane F, Loussaief C, Salem R, Toumi A, Belhadjali H, Chaabane A, Boughattas NA, Chakroun M Tags: J Clin Pharmacol Source Type: journals

Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Panitumumab is a fully human monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor (EGFR). A comprehensive population pharmacokinetic model of panitumumab was developed using nonlinear mixed-effects modeling of 1200 patients with advanced solid tumors in 14 clinical studies. The disposition of panitumumab was best described with a 2-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination pathways. For a typical male patient with colorectal cancer (80 kg, 60 years old), the estimates for the linear clearance (CL), the maximum nonlinear clearance (V...
Source: The Journal of Clinical Pharmacology - August 31, 2009 Category: Drugs & Pharmacology Authors: Ma P, Yang BB, Wang YM, Peterson M, Narayanan A, Sutjandra L, Rodriguez R, Chow A Tags: J Clin Pharmacol Source Type: journals

Model-Based Evaluation of QTc Interval Risk: An Increasing Emphasis on Early Decision Making.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19717724 [PubMed - in process] (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - August 31, 2009 Category: Drugs & Pharmacology Authors: Krishna R Tags: J Clin Pharmacol Source Type: journals

Human pharmacokinetics/pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pitrakinra, a 15-kDa recombinant human interleukin-4 mutein, targets allergic Th2 inflammation by competitively binding to interleukin-4 receptor alpha to interfere with interleukin-4 and interleukin-13 action. The authors characterized pitrakinra pharmacokinetics using data from 96 atopic patients, then compared pharmacokinetics with pharmacological response in asthma following subcutaneous versus inhalation dosing. A 1-compartment systemic model with site-specific absorption describes pitrakinra pharmacokinetics following subcutaneous, nebulization, and inhalation powder delivery. Typical CL/F and V/F, referenced to ...
Source: The Journal of Clinical Pharmacology - August 31, 2009 Category: Drugs & Pharmacology Authors: Burmeister Getz E, Fisher DM, Fuller R Tags: J Clin Pharmacol Source Type: journals

The Effect of Raltegravir on the Glucuronidation of Lamotrigine.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The authors studied the effect of raltegravir on the pharmacokinetics of the antiepileptic agent lamotrigine. Twelve healthy volunteers (group A) received 400 mg raltegravir twice daily from days 1 to 5. On day 4, a single dose of 100 mg lamotrigine was administered. After a washout period, participants received a second single dose of 100 mg of lamotrigine but now without raltegravir (day 32). In group B, 12 participants received the same treatment as in group A but in reverse order. On days 4 and 32, 48-hour pharmacokinetic curves were drawn. Geometric mean ratios (+90% confidence intervals [CIs]) of lamotrigine area...
Source: The Journal of Clinical Pharmacology - August 27, 2009 Category: Drugs & Pharmacology Authors: van Luin M, Colbers A, Verwey-van Wissen CP, van Ewijk-Beneken-Kolmer EW, van der Kolk M, Hoitsma A, da Silva HG, Burger DM Tags: J Clin Pharmacol Source Type: journals

Electroporation as an Efficient Physical Enhancer for Skin Drug Delivery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of high-voltage pulses to the skin increases its permeability (electroporation) and enables the delivery of various substances into and through the skin. The application of electroporation to the skin has been shown to increase transdermal drug delivery. Moreover, electroporation, used alone or in combination with other enhancement methods, expands the range of drug...
Source: The Journal of Clinical Pharmacology - August 27, 2009 Category: Drugs & Pharmacology Authors: Escobar-Chávez JJ, Bonilla-Martí Nez D, Villegas-González MA, Revilla-Vázquez AL Tags: J Clin Pharmacol Source Type: journals

Single- and Multiple-Dose Pharmacokinetics and Dose Proportionality of the Psychotropic Agent Paliperidone Extended Release.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Paliperidone extended-release tablet (paliperidone ER) is a centrally active dopamine D2- and serotonergic 5-HT2A-receptor antagonist that is registered for the treatment of schizophrenia. The controlled rate of release of paliperidone from the ER formulation is designed to have a slower absorption rate, which results in gradual ascending plasma concentrations with observed maximum plasma concentrations occurring at 24 hours after dosing on the first dosing day. On subsequent treatment days, the ER formulation provides minimal fluctuations in plasma concentrations. Paliperidone is eliminated with a terminal half-life o...
Source: The Journal of Clinical Pharmacology - August 26, 2009 Category: Drugs & Pharmacology Authors: Boom S, Talluri K, Janssens L, Remmerie B, De Meulder M, Rossenu S, van Osselaer N, Eerdekens M, Cleton A Tags: J Clin Pharmacol Source Type: journals