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Structure-pharmacokinetic relationship of in vivo rat biliary excretionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, in vivo rat biliary excretion of drug-like molecules was measured using bile duct cannulated rats. Literature biliary excretion data with similar experimental conditions were collected. A predictive quantitative structure-pharmacokinetic relationship (QSPR) model was developed using genetic algorithm guided principal component regression analysis and 2D molecular descriptors. In the derived model, hydrophobicity expressed with calculated distribution coefficients (cLogD) is the most important molecular property correlating biliary excretion. The derived model has been validated using literature data, and sho...
Source: Biopharmaceutics and Drug Disposition - November 11, 2009 Category: Drugs & Pharmacology Authors: Yue Chen, Kimberly Cameron, Angel Guzman-Perez, David Perry, Dong Li, Hua Gao Source Type: journals

In vitro-in vivo correlation for nevirapine extended release tabletsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An in vitro-in vivo correlation (IVIVC) for four nevirapine extended release tablets with varying polymer contents was developed. The pharmacokinetics of extended release formulations were assessed in a parallel group study with healthy volunteers and compared with corresponding in vitro dissolution data obtained using a USP apparatus type 1. In vitro samples were analysed using HPLC with UV detection and in vivo samples were analysed using a HPLC-MS/MS assay; the IVIVC analyses comparing the two results were performed using WinNonlin®. A Double Weibull model optimally fits the in vitro data. A unit impulse response (UIR)...
Source: Biopharmaceutics and Drug Disposition - October 30, 2009 Category: Drugs & Pharmacology Authors: Sreeraj Macha, Chan-Loi Yong, Todd Darrington, Mark S. Davis, Thomas R. MacGregor, Mark Castles, Steven L. Krill Source Type: journals

Effects of obesity induced by high-fat diet on the pharmacokinetics of nelfinavir, a HIV protease inhibitor, in laboratory ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The effect of obesity induced by a high-fat diet on the pharmacokinetics (PK) of nelfinavir (NFV) was investigated, focusing on the change of distribution and elimination caused by dyslipidemia and hepatic steatosis.The plasma unbound fraction (fu) of NFV in obese rats (0.61±0.03%) was significantly lower than in the control (1.10±0.09%), caused by increasing the plasma triglyceride-rich lipoprotein level. After intravenous (i.v.) administration of NFV, the marked decrease of the distribution volume and slower total clearance (39.5% and 69.1% of the control, respectively) caused by the lower fu were the main reasons for ...
Source: Biopharmaceutics and Drug Disposition - October 28, 2009 Category: Drugs & Pharmacology Authors: Nobuyuki Sugioka, Kenta Haraya, Keizo Fukushima, Yukako Ito, Kanji Takada Source Type: journals

Pharmacokinetics, bioavailability and effects on electrocardiographic parameters of oral fludarabine phosphateEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pharmacokinetics, bioavailability and effects on electrocardiographic (ECG) parameters of fludarabine phosphate (2F-ara-AMP) were evaluated in adult patients with B-cell chronic lymphocytic leukemia. Patients received single doses of intravenous (IV) (25 mg/m2, n=14) or oral (40 mg/m2, n=42) 2F-ara-AMP. Plasma concentrations of drug and metabolites and digital 12-lead ECGs were monitored for 23 h after dosing. The dephosphorylated product fludarabine (2F-ara-A) was the principal metabolite present in the systemic circulation. Mean (±SD) elimination half-life did not differ significantly between IV and oral dosage grou...
Source: Biopharmaceutics and Drug Disposition - October 27, 2009 Category: Drugs & Pharmacology Authors: Wei Yin, Elena V. Karyagina, Ante S. Lundberg, David J. Greenblatt, John Lister-James Source Type: journals

In vitro-in vivo correlation of modified release dosage form of lamotrigineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The plasma concentration profile of lamotrigine was predicted from the dissolution test data of the modified release 100 mg lamotrigine tablet by applying the in vitro-in vivo correlation (IVIVC). Three different release formulations (L-1, L-2 and L-3) and its profiles of in vitro data were generated in different dissolution media. Pharmacokinetics evaluation of these formulations was carried out in 12 healthy volunteers. In vitro-in vivo correlation was established from the generated dissolution and bioavailability data. A good correlation between the percentages dissolved vs absorbed (r2>0.989) was obtained using level A...
Source: Biopharmaceutics and Drug Disposition - October 11, 2009 Category: Drugs & Pharmacology Authors: Hiten J. Shah, Gunta Subbaiah, Dasharath M. Patel, Chhagan N. Patel Source Type: journals

Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Carnitine/organic cation transporter 2 (OCTN2) recognizes various cationic compounds as substrates in vitro, but information on its pharmacokinetic role in vivo is quite limited. This paper demonstrates altered tissue distribution of the OCTN2 substrate pyrilamine in juvenile visceral steatosis (jvs) mice, which have a hereditary defect of the octn2 gene. At 30 min after intravenous injection of pyrilamine, the tissue-to-plasma concentration ratio (Kp) in the heart and pancreas was higher, whereas the Kp in kidney and testis was lower in jvs mice compared with wild-type mice. Pyrilamine transport studies in isolated heart ...
Source: Biopharmaceutics and Drug Disposition - October 8, 2009 Category: Drugs & Pharmacology Authors: Sayaka Kato, Yukio Kato, Tadakatsu Nakamura, Tomoko Sugiura, Yoshiyuki Kubo, Yoshiharu Deguchi, Akira Tsuji Source Type: journals

The assessment of human regional drug absorption of free acid and sodium salt forms of Acipimox, in healthy volunteers, to direct modified release formulation strategyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non-randomized, three-way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediat...
Source: Biopharmaceutics and Drug Disposition - September 30, 2009 Category: Drugs & Pharmacology Authors: Rajeev Menon, Eugenio Cefali, Ian Wilding, Heather Wray, Alyson Connor Source Type: journals

Effect of itraconazole on the pharmacokinetics of everolimus administered by different routes in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, intraintestinally administered itraconazole dramatically increased the AUC of everolimus delivered intraintestinally by inhibiting the intestinal first-pass extraction of this drug. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 29, 2009 Category: Drugs & Pharmacology Authors: Akira Yokomasu, Ikuko Yano, Eriko Sato, Satohiro Masuda, Toshiya Katsura, Ken-ichi Inui Source Type: journals

Pharmacokinetic behavior of huperzine A in plasma and cerebrospinal fluid after intranasal administration in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim of this study was to investigate the pharmacokinetic behavior of huperzine A (Hup A) in plasma and cerebrospinal fluid (CSF) after intranasal administration (0.5 mg/kg) in male Sprague-Dawley rats. A pharmacokinetic study of intravenous Hup A (0.5 mg/kg) was also performed. The concentrations of Hup A in the biological samples were measured by high performance liquid chromatography-mass spectrometry. Blood samples were taken from the tail vein and CSF was sampled by cisternal puncture using a stereotaxic frame. The contribution of the olfactory pathway to the uptake of Hup A into CSF was determined by comparing the...
Source: Biopharmaceutics and Drug Disposition - September 24, 2009 Category: Drugs & Pharmacology Authors: Qiao Wang, Guoshen Chen Source Type: journals

Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI 1356) - investigations in DPP-4 deficient and wildtype ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, the study showed that the concentration-dependent binding of linagliptin to its target DPP-4 has a major impact on the plasma pharmacokinetics of linagliptin. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 21, 2009 Category: Drugs & Pharmacology Authors: Silke Retlich, Barbara Withopf, Andreas Greischel, Alexander Staab, Ulrich Jaehde, Holger Fuchs Source Type: journals

A comparison of uptake of metformin and phenformin mediated by hOCT1 in human hepatocytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study for the first time produced detailed comparative findings for uptake profiles of metformin and phenformin in human hepatocytes and hOCT1 expressing oocytes. It is considered that hOCT1 may not be the only key factor that determines the frequency of metformin and phenformin toxicity, considering the major contribution of this transporter to the total hepatic uptake and comparable width of their therapeutic concentrations. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 17, 2009 Category: Drugs & Pharmacology Authors: Yoshihisa Sogame, Atsushi Kitamura, Masashi Yabuki, Setsuko Komuro Source Type: journals

Time-dependent effects of Klebsiella pneumoniae endotoxin on the pharmacokinetics of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, in rats: restoration of the parameters in 96 hour in KPLPS rats to control levelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It has been reported that chlorzoxazone (CZX) was primarily metabolized via hepatic Cyp2e1 to form 6-hydroxychlorzoxazone (OH-CZX) in rats, and the activity of aniline hydroxylase (a Cyp2e1 marker) in the liver was significantly decreased in rats at 24 h after pretreatment with lipopolysaccharide derived from Klebsiella pneumoniae (24 h KPLPS rats), whereas the levels were not changed at 2 h and 96 h in the KPLPS rats. Thus, the time-dependent pharmacokinetic parameters of CZX and OH-CZX were evaluated after the intravenous administration of CZX (20 mg/kg) to control rats, and the 2 h, 24 h and 96 h KPLPS rats along with t...
Source: Biopharmaceutics and Drug Disposition - September 14, 2009 Category: Drugs & Pharmacology Authors: Hye Y. Jung, Hee E. Kang, Young H. Choi, So H. Kim, Myung G. Lee Source Type: journals

1[alpha],25-dihydroxyvitamin D3 triggered vitamin D receptor and farnesoid X receptor-like effects in rat intestine and liver in vivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
1[alpha],25-Dihydroxyvitamin D3 (1,25(OH)2D3), a natural ligand of the vitamin D receptor (VDR), was found to increase the rat ileal Asbt and bile acid absorption. The effects of VDR, whose expression is low in liver, on hepatic transporters and enzymes are unknown. Protein and mRNA levels of target genes in the small intestine, colon and liver after intraperitoneal dosing of 1,25(OH)2D3 (0-2.56 nmol/kg/day for 4 days) to the rat were determined by Western blotting and qPCR, respectively. The 1,25(OH)2D3 treatment increased total Cyp3a protein and Cyp3a1 mRNA expressions in the proximal small intestine, and the short heter...
Source: Biopharmaceutics and Drug Disposition - September 13, 2009 Category: Drugs & Pharmacology Authors: Edwin C. Y. Chow, Han-Joo Maeng, Shanjun Liu, Ansar A. Khan, Geny M. M. Groothuis, K. Sandy Pang Source Type: journals

Comparative gene expression of intestinal metabolizing enzymesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by...
Source: Biopharmaceutics and Drug Disposition - September 9, 2009 Category: Drugs & Pharmacology Authors: Ho-Chul Shin, Hye-Ryoung Kim, Hee-Jung Cho, Hee Yi, Soo-Min Cho, Dong-Goo Lee, A. M. Abd El-Aty, Jin-Suk Kim, Duxin Sun, Gordon L. Amidon Source Type: journals

High dose methotrexate population pharmacokinetics and Bayesian estimation in patients with lymphoid malignancyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of present study was to develop a population pharmacokinetic model of high dose methotrexate (HD-MTX) infusion in patients with lymphoid malignancy, to investigate the biological and clinical covariates related to the drug distribution and elimination. It is also the purpose to propose a limited sampling strategy (LSS) for the estimation of the time above the threshold (0.2 µmol·L-1). A total 82 patients with lymphoid malignancy were involved in the study. A pharmacokinetic model was developed using nonlinear mixed-effect model. The influence of demographic characteristics, biological factors, and concurrent ...
Source: Biopharmaceutics and Drug Disposition - September 8, 2009 Category: Drugs & Pharmacology Authors: Ye Min, Fu Qiang, Li Peng, Zhu Zhu Source Type: journals

A 1-step Bayesian predictive approach for evaluating in vitro in vivo correlation (IVIVC)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IVIVC (in vitro in vivo correlation) methods may support approving a change in formulation of a drug using only in vitro dissolution data without additional bioequivalence trials in human subjects. Most current IVIVC methods express the in vivo plasma concentration of a drug formulation as a function of the cumulative in vivo absorption. The absorption is not directly observable, so is estimated by the cumulative dissolution of the drug formulation in in vitro dissolution trials. The calculations conventionally entail the complex and potentially unstable mathematical operations of convolution and deconvolution, or approxim...
Source: Biopharmaceutics and Drug Disposition - September 3, 2009 Category: Drugs & Pharmacology Authors: A. Lawrence Gould, Nancy G. B. Agrawal, Thanh V. Goel, Shaun Fitzpatrick Source Type: journals

Temperature-dependent specific transport of levofloxacin in human intestinal epithelial LS180 cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It was reported previously that specific levofloxacin uptake in Caco-2 cells was inhibited by nicotine, enalapril, L-carnitine and fexofenadine. The aim of the present study was to characterize the cellular uptake of levofloxacin using another human intestinal cell line, LS180. Levofloxacin uptake in LS180 cells was temperature-dependent and optimal at neutral pH, but was Na+-independent. The rank order of inhibitory effects of the four compounds on [14C] levofloxacin uptake in LS180 cells was nicotine>enalapril>L-carnitine>fexofenadine, which is consistent with that in Caco-2 cells. The mRNA levels of OATP1A2, 1B1, 1B3 an...
Source: Biopharmaceutics and Drug Disposition - August 31, 2009 Category: Drugs & Pharmacology Authors: Shiro Fukumori, Miki Masago, Kazuya Ishida, Yuichiro Kayano, Masato Taguchi, Yukiya Hashimoto Source Type: journals

Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transportersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The nuclear transcription factor E2-related factor 2 (Nrf2) has been shown to play pivotal roles in preventing xenobiotic-related toxicity and carcinogen-induced carcinogenesis. These protective roles of Nrf2 have been attributed in part to its involvement in the induction of Phase II drug conjugation/detoxification enzymes as well as antioxidant enzymes through the Nrf2-antioxidant response element (ARE) signaling pathways. This review summarizes the current research status of the identification of Nrf2-regulated drug metabolism enzymes (DMEs), especially Phase II DMEs, and Phase III drug transporters. In addition, the mo...
Source: Biopharmaceutics and Drug Disposition - August 30, 2009 Category: Drugs & Pharmacology Authors: Guoxiang Shen, Ah-Ng Kong Source Type: journals

Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study was to compare the hepatic and small intestinal metabolism, and to examine bioavailability and gastro-intestinal first-pass effects, of kaempferol in rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of kaempferol for up to 120 min. Based on the values of the kinetic constants (Km and Vmax), the propensity for UDPGA-dependent conjugation compared with NADPH-dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague-Dawley rats were administered kaempferol intravenously (i.v.) (10...
Source: Biopharmaceutics and Drug Disposition - August 30, 2009 Category: Drugs & Pharmacology Authors: Avantika Barve, Chi Chen, Vidya Hebbar, Joseph Desiderio, Constance Lay-Lay Saw, Ah-Ng Kong Source Type: journals

Influence of Coptis Chinensis on pharmacokinetics of flavonoids after oral administration of Radix Scutellariae in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Radix Scutellariae (RS) and Coptis Chinensis (CC) are the most popular components in traditional Chinese medicine prescriptions. Flavonoids are the main effective ingredients in RS and berberine is the main effective ingredient in CC. The aim of this study was to determine the influence of CC on the pharmacokinetics of flavonoids following the administration of RS in rats and to investigate the effects of CC on the pharmacokinetic mechanism. Rats were administered RS or RS+CC by intragastric gavage (ig). Plasma concentrations of baicalin (baicalein 7-glucuronide) and wogonoside (wogonin 7-glucuronide) were measured by HPLC...
Source: Biopharmaceutics and Drug Disposition - August 16, 2009 Category: Drugs & Pharmacology Authors: Rong Shi, Hui Zhou, Zhaoming Liu, Yueming Ma, Tianming Wang, Yingying Liu, Changhong Wang Source Type: journals

Stability of cucurbitacin E in human plasma: chemical hydrolysis and role of plasma esterasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the biochemical stability of Cuc E was investigated in vitro by reverse-phase high performance liquid chromatography. The hydrolysis rate in acidic and alkaline solutions, and in enzymatic conditions in human plasma and in purified plasma esterase solutions of butyrylcholinesterase and albumin, was compared with that measured in phosphate buffer saline (pH 7.4).Cuc E hydrolysis was detected in all the in vitro tests, but the extent of hydrolysis varied according to the different enzymatic and non-enzymatic conditions. A remarkable rapid hydrolysis of Cuc E was detected in acidic and alkaline solutions. A sig...
Source: Biopharmaceutics and Drug Disposition - August 15, 2009 Category: Drugs & Pharmacology Authors: Myriam Saade, Jacques Magdalou, Naim Ouaini, Helene Greige-Gerges Source Type: journals

Estimation of intragastric drug solubility in the fed state: comparison of various media with data in aspiratesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The suitability of various media to forecast the solubility of ketoconazole and dipyridamole in the fed stomach at various periods after meal administration was evaluated. Solubilities were measured with the shake-flask method in gastric fluids aspirated 30, 60 and 120 min after administration of 500 ml Ensure plus® to healthy fasted adults, in three sets of simulated gastric fluids based on milk, and in simple aqueous buffered media. Simple aqueous buffered media vastly underestimated the intragastric solubility of model compounds in the fed state. When using undigested milk-based media, the solubilities of model compoun...
Source: Biopharmaceutics and Drug Disposition - July 29, 2009 Category: Drugs & Pharmacology Authors: A. Diakidou, M. Vertzoni, J. Dressman, C. Reppas Source Type: journals

Mechanisms responsible for the altered pharmacokinetics of Bosentan: analysis utilizing rats with bile duct ligation-induced liver dysfunctionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study was to evaluate the mechanisms responsible for the pharmacokinetic variability of bosentan utilizing rats with liver dysfunction induced by 7-day bile duct ligation (BDL). Bosentan was administered intravenously at a constant infusion rate (I) of 24, 40 or 60 µg/min/kg. The blood bosentan concentration (BBC) following infusion was measured by HPLC, and apparent clearance (CL) of the drug was estimated as I/BBC. The CL values in normal rats were 30.5 and 19.3 ml/min/kg at infusion rates of 24 and 60 µg/min/kg, respectively, suggesting non-linear pharmacokinetics of bosentan. The BBC in BDL rats w...
Source: Biopharmaceutics and Drug Disposition - July 28, 2009 Category: Drugs & Pharmacology Authors: Isao Horiuchi, Yun-i Mori, Masato Taguchi, Fukiko Ichida, Toshio Miyawaki, Yukiya Hashimoto Source Type: journals

Dose-dependent pharmacokinetics and first-pass effects of mirodenafil, a new erectogenic, in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous (5, 10, 20 and 50 mg/kg) and oral (10, 20 and 50 mg/kg) administration of mirodenafil, and the first-pass effect of mirodenafil after intravenous, oral, intraportal, intragastric and intraduodenal (20 mg/kg) administration of mirodenafil were evaluated in rats. The pharmacokinetics of mirodenafil and SK3541 were dose-dependent after both intravenous and oral administration of mirodenafil due to the saturable hepatic metabolism of mirodenafil. After oral administration of mirodenafil, approximately 2.59% of the oral dose was no...
Source: Biopharmaceutics and Drug Disposition - July 27, 2009 Category: Drugs & Pharmacology Authors: Young H. Choi, Young S. Lee, Soo H. Bae, Tae K. Kim, Bong-Y. Lee, Myung G. Lee Source Type: journals

ABC transporters and isothiocyanates: potential for pharmacokinetic diet-drug interactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Isothiocyanates, a class of anti-cancer agents, are derived from cruciferous vegetables such as broccoli, cabbage and watercress, and have demonstrated chemopreventive activity in a number of cancer models and epidemiologic studies. Due to public interest in cancer prevention and alternative therapies in cancer, the consumption of herbal supplements and vegetables containing these compounds is widespread and increasing. Isothiocyanates interact with ATP-binding cassette (ABC) efflux transporters such as P-glycoprotein, MRP1, MRP2 and BCRP, and may influence the pharmacokinetics of substrates of these transporters. This rev...
Source: Biopharmaceutics and Drug Disposition - July 21, 2009 Category: Drugs & Pharmacology Authors: Urvi Telang, Yan Ji, Marilyn E. Morris Source Type: journals

Quantification and prediction of skin pharmacokinetics of amoxicillin and cefuroximeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, this study shows that it is possible to generate a reasonable prediction of skin pharmacokinetics from any plasma level once a careful characterization of the transfer process between plasma and skin has been made. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - July 10, 2009 Category: Drugs & Pharmacology Authors: Chinmay Shukla, Vishal Patel, Ravi Juluru, Grazia Stagni Source Type: journals

Ipriflavone pharmacokinetics in mutant Nagase analbuminemic ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the contribution of hepatic CYP2C11 and intestinal CYP1A protein to the metabolism and the pharmacokinetic parameters of ipriflavone were examined after intravenous (20 mg/kg) and oral (200 mg/kg) administration to male Sprague-Dawley (control) rats and NARs. There was no change in the protein expression of hepatic CYP2C11. By contrast, CYP1A protein of the intestine increased by almost 100%. After the intravenous administration of ipriflavone to NARs, the Clnr and AUC were unchanged, suggesting that the contribution of the increase in protein expression and mRNA level of hepatic CYP1A2 to hepatic metabolism...
Source: Biopharmaceutics and Drug Disposition - July 8, 2009 Category: Drugs & Pharmacology Authors: Hye J. Chung, Hee E. Kang, Kyung H. Yang, Sung Y. Kim, Myung G. Lee Source Type: journals

Artemisinin-a possible CYP2B6 probe substrate?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Aim. To compare in vitro metabolism rates for artemisinin and the CYP2B6 substrates, bupropion, propofol and efavirenz in human liver microsomes.Methods. Rate constants of artemisinin, bupropion, propofol and efavirenz metabolism by human liver microsomes from a panel of 12 donors, with different levels of CYP2B6 activity, were estimated in WinNonlin. Correlations between the metabolic rate constant for artemisinin and the other CYP2B6 substrates were examined.Results. Artemisinin and propofol depletion data in human liver microsomes were described by first order kinetic models. For bupropion and efavirenz, metabolite form...
Source: Biopharmaceutics and Drug Disposition - June 24, 2009 Category: Drugs & Pharmacology Authors: Sara Asimus, Michael Ashton Tags: Original Papers Source Type: journals

Transport characteristics of candesartan in human intestinal Caco-2 cell lineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The intestinal absorptive characteristics and the efflux mechanisms of candesartan (CDS), a novel angiotensin II type 1 receptor blocker, were investigated. The Caco-2 cells were used as models of the intestinal mucosa to assess uptake and transport of CDS. The determination of CDS was performed by HPLC-Flu. In the Caco-2 cells, the uptake and absorptive transport of CDS were pH-independent (in the pH range 6.0-8.0). Passive membrane diffusion dominates the absorptive transport behavior of CDS across Caco-2 cells, while secretory transport was a concentration-dependent and saturable process. In the presence of cyclosporin ...
Source: Biopharmaceutics and Drug Disposition - June 24, 2009 Category: Drugs & Pharmacology Authors: Lingjie Zhou, Xiaoping Chen, Yuanqing Gu, Jianying Liang Tags: Original Papers Source Type: journals

Expression and regulation of the bile acid transporter, OST[alpha]-OST[beta] in rat and human intestine and liverEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study suggest that, apart from FXR ligands, the OST[alpha] and OST[beta] genes are also regulated by VDR and GR ligands and not by PXR ligands. This study show that VDR ligands exerted different effects on OST[alpha]-OST[beta] in the rat and human intestine and liver compared with other nuclear receptors, FXR, PXR, and GR, pointing to species- and organ-specific differences in the regulation of OST[alpha]-OST[beta] genes. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 24, 2009 Category: Drugs & Pharmacology Authors: Ansar A. Khan, Edwin C. Y. Chow, Robert J. Porte, K. Sandy Pang, Geny M. M. Groothuis Tags: Original Papers Source Type: journals

Tissue distribution of the novel DPP-4 inhibitor BI 1356 is dominated by saturable binding to its target in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigated whether saturable binding of BI 1356 to its target DPP-4 occurs in tissues and whether drug accumulation occurs at these sites in vivo. In order to test these hypotheses, the tissue distribution of BI 1356 was determined in wild-type and DPP-4 deficient rats at different dose levels by means of whole body autoradiography and measurement of tissue radioactivity concentrations after single i.v. dosing of [14C]-radio labeled BI 1356. The accumulation behavior of drug-related radioactivity in tissues was further explored in an oral repeat dose study. Tissue levels of [14C]BI 1356 related radioactivity w...
Source: Biopharmaceutics and Drug Disposition - June 24, 2009 Category: Drugs & Pharmacology Authors: Holger Fuchs, Rudolf Binder, Andreas Greischel Tags: Original Papers Source Type: journals

Evaluation of the effect of intravenous volume expanders upon the volume of distribution of gentamicin in septic neonatesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sepsis has been reported to increase the volume of distribution of gentamicin in neonates. To determine whether this was caused by the use of intravenous volume expanders a retrospective nested case-control study was performed comparing confirmed septic neonates with non-septic controls. Data were collected on intravenous administration of 0.45% saline/10% dextrose, 0.45% saline/5% dextrose, 0.9% normal saline, red blood cells, platelets, immunoglobulin (Intragam P) and albumin. A population pharmacokinetic analysis was performed using NONMEM for 116 neonates (29 confirmed septic) from which 363 gentamicin serum concentrat...
Source: Biopharmaceutics and Drug Disposition - June 24, 2009 Category: Drugs & Pharmacology Authors: Catherine M. T. Sherwin, Esther Kostan, Roland S. Broadbent, Natalie J. Medlicott, David M. Reith Source Type: journals

Pharmacokinetics of caffeic acid phenethyl ester and its catechol-ring fluorinated derivative following intravenous administration to ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pharmacokinetic profiles of caffeic acid phenethyl ester (CAPE) and its catechol-ring fluorinated derivative (FCAPE) were determined in rats after intravenous administration of 5, 10 or 20 mg/kg for CAPE and 20 mg/kg for FCAPE, respectively. The plasma concentrations of CAPE and FCAPE were measured using a validated liquid chromatography tandem mass spectrometric method. The pharmacokinetic parameters were estimated using non compartmental analysis (NCA) and biexponential fit. The results showed that the area under the plasma concentration-time curve for CAPE treatment increased in a proportion greater than the increas...
Source: Biopharmaceutics and Drug Disposition - June 16, 2009 Category: Drugs & Pharmacology Authors: Xinyu Wang, Jihai Pang, Jacqueline A. Maffucci, Devendra S. Pade, Robert A. Newman, Sean M. Kerwin, Phillip D. Bowman, Salomon Stavchansky Source Type: journals

Pharmacokinetics of sertindole and its metabolite dehydrosertindole in rats and characterization of their comparative pharmacodynamics based on in vivo D2 receptor occupancy and behavioural conditioned avoidance responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objectives of this study were to characterize the pharmacokinetics of sertindole and its active metabolite dehydrosertindole in rats and to evaluate the central modulatory and behavioural pharmacodynamics including a competitive interaction model between the compounds. Following oral administration of sertindole or dehydrosertindole, the plasma concentration-time courses were determined in conjunction with striatal dopamine D2 receptor binding. In addition, the behavioural effects were recorded in the conditioned avoidance response (CAR) paradigm. A one-compartment model with Michaelis-Menten elimination best described...
Source: Biopharmaceutics and Drug Disposition - May 27, 2009 Category: Drugs & Pharmacology Authors: Christoffer Bundgaard, Frank Larsen, Mads Kreilgaard, Lise T. Brennum, Christina Kurre Olsen Source Type: journals

In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pigEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24 h, followed by sequential collection of blood specimens from 0 to 36 h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12 h after the application (n=4). Ketoprofen was first detected in the plasma at 8 h, the concentration increasing up to 24 h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprof...
Source: Biopharmaceutics and Drug Disposition - May 15, 2009 Category: Drugs & Pharmacology Authors: Masafumi Horie, Ichiro Sekiya, Tomomasa Nakamura, Hozumi Tanaka, Kotaro Maekawa, Masaru Nakanishi, Takeshi Muneta, Eiji Kobayashi Source Type: journals

An improved high-performance liquid chromatography method for quantification of methotrexate polyglutamates in red blood cells of children with juvenile idiopathic arthritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Methotrexate is used widely in the pharmacotherapy of juvenile idiopathic arthritis. Polyglutamates of methotrexate are active metabolites which accumulate in cells including erythrocytes. Their intracellular concentration may reflect methotrexate bioavailability and, at the same time, may serve as a bioindicator for optimization of methotrexate therapy and drug monitoring. Therefore, a simple and selective isocratic reversed phase chromatographic method with fluorescence detection (excitation/emission wavelengths of 370/463 nm) was developed which quantifies the sum of all methotrexate polyglutamates in erythrocytes as me...
Source: Biopharmaceutics and Drug Disposition - March 25, 2009 Category: Drugs & Pharmacology Authors: Milo[scaron] Hroch, Jana Tuková, Pavla Dole[zcaron]alová, Jaroslav Chládek Tags: Original Papers Source Type: journals

Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
L-Citrulline has diagnostic potential for renal function, because its plasma concentration increases with the progression of renal failure. Although L-citrulline extracted by glomerular filtration in kidney is mostly reabsorbed, the mechanism involved is not clearly understood. The present study was designed to characterize L-citrulline transport across the apical membranes of renal epithelial tubular cells, using primary-cultured rat renal proximal tubular cells, as well as the human kidney proximal tubular cell line HK-2. L-Citrulline was transported in a Na+-dependent manner from the apical side of both cell types cultu...
Source: Biopharmaceutics and Drug Disposition - March 25, 2009 Category: Drugs & Pharmacology Authors: Keisuke Mitsuoka, Yoshiyuki Shirasaka, Akimasa Fukushi, Masanobu Sato, Toshimichi Nakamura, Takeo Nakanishi, Ikumi Tamai Tags: Original Papers Source Type: journals

Noncompartmental pharmacokinetics analysis of glucose-stimulated insulin response in African-American and Caucasian youthsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of this study was to examine the differences in glucose and insulin responses between African-American and Caucasian youths and to determine the associations of between-group differences with sex, body mass index (BMI) and pubertal status using a noncompartmental pharmacokinetic approach. Sixteen African-American and 22 Caucasian healthy adolescents were tested using the frequently sampled intravenous glucose tolerance test. Longitudinal t-tests across each observation revealed that (1) African-American youths have higher insulin concentrations between 4 to 19 min; (2) insulin levels remained similar as subje...
Source: Biopharmaceutics and Drug Disposition - March 17, 2009 Category: Drugs & Pharmacology Authors: Lanyi Xie, R. P. Hoffman, Peter Veng-Pedersen Source Type: journals

Faster clearance of omeprazole in mutant Nagase analbuminemic rats: possible roles of increased protein expression of hepatic CYP1A2 and lower plasma protein bindingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is well known that there are various changes in the expression of hepatic and intestinal CYPs in mutant Nagase analbuminemic rats (NARs). It has been reported that the protein expression of hepatic CYP1A2 was increased, whereas that of hepatic CYP3A1 was not altered, and it was also found that the protein expression of the intestinal CYP1A subfamily significantly increased in NARs from our other study. In addition, in this study additional information about CYP changes in NARs was obtained; the protein expression of the hepatic CYP2D subfamily was not altered, but that of the intestinal CYP3A subfamily increased in NARs...
Source: Biopharmaceutics and Drug Disposition - March 14, 2009 Category: Drugs & Pharmacology Authors: Dae Y. Lee, Young S. Jung, Young C. Kim, Sung Y. Kim, Myung G. Lee Source Type: journals

Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - March 4, 2009 Category: Drugs & Pharmacology Authors: Simin O. Mashayekhi, Mohammadreza Ghandforoush-Sattari, Philip A. Routledge, Richard D.W. Hain Source Type: journals

Expression levels of human P-glycoprotein in In Vitro cell lines: correlation between mRNA and protein levels for P-glycoprotein expressed in cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this study was to investigate the correlation between mRNA and protein levels for P-glycoprotein (P-gp) expressed in various cell lines to validate the estimation of P-gp activity from its mRNA levels. P-gp expression levels in various cell monolayers, normal, P-gp-induced, P-gp-highly induced, (multidrug resistance, MDR) MDR1-knockdown (A2-2) and MDR1-knockdown (B2-2) Caco-2 cells and MDCKII/MDR1 cells, were quantified by real-time quantitative polymerase chain reaction (PCR) and western blot analysis. Both mRNA and protein levels of P-gp were lowest in the MDR1-knockdown (B2-2) Caco-2 cells, followed by th...
Source: Biopharmaceutics and Drug Disposition - March 2, 2009 Category: Drugs & Pharmacology Authors: Yoshiyuki Shirasaka, Reiko Konishi, Nana Funami, Yuko Kadowaki, Yuri Nagai, Toshiyuki Sakaeda, Shinji Yamashita Source Type: journals

Influence of formulation factors on PpIX production and photodynamic action of novel ALA-loaded microparticlesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A novel 5-aminolevulinic acid (ALA)-containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to the skin of living animals, followed by study of protoporphyrin IX (PpIX) production. The effect of formulating the microparticles in different vehicles was investigated and also the phototoxicity of the PpIX produced using a model tumour.Particles formulated in propylene glycol gels (10% w/w ALA loading) gen...
Source: Biopharmaceutics and Drug Disposition - February 20, 2009 Category: Drugs & Pharmacology Authors: Ryan F. Donnelly, Paul A. McCarron, Rasil Al-Kassas, Asta Juzeniene, Petras Juzenas, Vladimir Iani, A. David Woolfson, Johan Moan Tags: Original Papers Source Type: journals

Biliary clearance of bromosulfophthalein in anesthetized and freely moving conscious ratEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim of this study was to investigate the effect of anesthesia on the pharmacokinetics of bromosulfophthalein (BSP) with focus on biliary clearance. The plasma concentration profile and biliary clearance of intravenously administered BSP was compared in conscious freely moving bile duct catheterized rats and rats anesthetized with ketamine or Zoletil. The plasma concentration of BSP in conscious rats was similar to that of anesthetized rats, irrespective of the anesthetic used. There was no significant difference in the volume of distribution, total body clearance and mean residence time of BSP between the groups. The b...
Source: Biopharmaceutics and Drug Disposition - February 19, 2009 Category: Drugs & Pharmacology Authors: Ju-Hee Oh, Se-Eun Park, Chang-Koo Shim, Young-Joo Lee Tags: Short Communications Source Type: journals

Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, 9 mg/kg verapamil was administered orally to Sprague-Dawley rats 30 min after the oral administration of 2 and 10 mg/kg of oral EGCG. Compared with the controls, the AUC values of both verapamil (74.3% and 111% increase for 2 and 10 mg/kg EGCG, respectively) and norverapamil (51.5% and 87.2% increase for 2 and 10 mg/kg EGCG, respectively) were significantly greater in the presence of EGCG. However, compared with the controls, both the AUC and the relative bioavailability of verapamil were significantly (p (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 19, 2009 Category: Drugs & Pharmacology Authors: Joong-Hwa Chung, Dong-Hyun Choi, Jun-Shik Choi Tags: Short Communications Source Type: journals

Pharmacokinetics of pyrrole-imidazole polyamides after intravenous administration in ratEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pharmacokinetics of pyrrole (Py)-imidazole (Im) polyamides was studied in rats after the intravenous administration of these compounds. Py-Im polyamide (A) was composed of Ac-ImPyPy-ImPyPy-[beta]-Dp ([beta]: [beta]-alanine, Dp: N,N-dimethylaminopropylamide). Py-Im polyamide (B) was composed of Ac-PyIm-[beta]-ImIm-PyPy-[beta]-PyPy-[beta]-Dp. Py-Im polyamide (C) was composed of Ac-PyPy-[beta]-PyImPy-PyPyPy-[beta]-ImPy-[beta]-Dp. The molecular weight of Py-Im polyamide (A) was 1035.12, that of Py-Im polyamide (B) was 1422.51 and that of Py-Im polyamide (C) was 1665.78. After the intravenous injection of Py-Im polyamide (A...
Source: Biopharmaceutics and Drug Disposition - February 19, 2009 Category: Drugs & Pharmacology Authors: Akiko Fukasawa, Takahiko Aoyama, Takashi Nagashima, Noboru Fukuda, Takahiro Ueno, Hiroshi Sugiyama, Hiroki Nagase, Yoshiaki Matsumoto Tags: Original Papers Source Type: journals

Investigation of some factors contributing to negative food effectsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the role of biopharmaceutical factors that contribute to negative food effects was studied using furosemide, nadolol, tacrine and atenolol (as model compounds exhibiting negative food effects), and prednisolone, hydrochlorothiazide and ibuprofen (as model compounds that do not show any food effects). The physiological pH of the upper intestinal tract is lower, at pH 5, in the postprandial state when compared with the preprandial state, pH 6.5. Drugs that exhibited negative food effects had low apical to basolateral Caco-2 permeabilities, low pKa/pKb and Log P values of less than 1. The drugs exhibiting negat...
Source: Biopharmaceutics and Drug Disposition - February 19, 2009 Category: Drugs & Pharmacology Authors: Venugopal P. Marasanapalle, John R. Crison, Jingwen Ma, Xiaoling Li, Bhaskara R. Jasti Tags: Original Papers Source Type: journals

Pharmacodynamics of glucose regulation by methylprednisolone. I. Adrenalectomized ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mechanisms related to the adverse effects of corticosteroids on glucose homeostasis were studied. Five groups of adrenalectomized (ADX) rats were given methylprednisolone (MPL) intravenously at 10 and 50 mg/kg, or a continuous 7 day infusion at rates of 0, 0.1, 0.3 mg/kg/h via subcutaneously implanted Alzet mini-pumps. Plasma concentrations of MPL, glucose and insulin were determined at various time points up to 72 h after injection or 336 h after infusion. The pharmacokinetics of MPL was captured with a two-compartment model. The Adapt II software was used in modeling. Injection of MPL caused a temporary glucose increase ...
Source: Biopharmaceutics and Drug Disposition - January 22, 2009 Category: Drugs & Pharmacology Authors: Jin Y. Jin, William J. Jusko Source Type: journals

Pharmacodynamics of glucose regulation by methylprednisolone. II. normal ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50 mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3 mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72 h after injection and 336 h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline ca...
Source: Biopharmaceutics and Drug Disposition - January 20, 2009 Category: Drugs & Pharmacology Authors: Jin Y. Jin, William J. Jusko Source Type: journals

Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increasedEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Peritoneal dialysis of a highly protein-bound compound, tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of tolbutamide increased. However, the efficacy of peritoneal dialysis of tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfamethoxazole treatment. When the unbound fraction of tolbutamide was increased 7.8 times by sulfadimethoxine...
Source: Biopharmaceutics and Drug Disposition - January 16, 2009 Category: Drugs & Pharmacology Authors: Takashi Makita, Tetsuya Aiba, Yuki Izuwa, Yukiko Komori, Hiromu Kawasaki, Yuji Kurosaki Source Type: journals

Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant-induced arthritis ratEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, a real-time reverse transcription-polymerase chain reaction was used to determine the effects of adjuvant-induced arthritis (AA) on the amounts of mRNA of 12 types of rat ATP-binding cassette (ABC) and solute carrier (SLC) transporters in the liver and small intestine, 7 (D7) and 21 days (D21) after the injection of adjuvant. There were no significant differences in mRNA levels of ABC and SLC transporters between the livers of AA and control rats on D7, except in the case of Mdr1a. However, levels of Mdr1a, Mrp2 and Oatp SLC transporters were significantly lower in AA than in the control livers on D21. In co...
Source: Biopharmaceutics and Drug Disposition - January 16, 2009 Category: Drugs & Pharmacology Authors: Satoshi Uno, Misato Uraki, Ayami Ito, Yuki Shinozaki, Ayano Yamada, Atsushi Kawase, Masahiro Iwaki Source Type: journals