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TKI combination therapy: strategy to enhance dasatinib uptake by inhibiting Pgp ‐ and BCRP‐mediated efflux
Abstract The overexpression of efflux transporters, especially P‐glycoprotein (Pgp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2), represents an important mechanism of multidrug resistance (MDR). Tyrosine kinase inhibitors (TKIs), a novel group of target‐specific anticancer drugs, have recently been found to interact with Pgp and BCRP and to serve as both substrates and inhibitors. Considering their dual role, we anticipate that combination TKI therapy may represent a promising strategy to reverse efflux transporter mediated TKI resistance. Presently, investigations on these interactions are very limi...
Source: Biopharmaceutics and Drug Disposition - September 12, 2016 Category: Drugs & Pharmacology Authors: Ronilda D'Cunha, SoHyun Bae, Daryl J. Murry, Guohua An Tags: Original Paper Source Type: research

Pre ‐incubation with cyclosporine a potentiates its inhibitory effects on pitavastatin uptake mediated by recombinantly expressed cynomolgus monkey hepatic organic anion transporting polypeptide
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 6, 2016 Category: Drugs & Pharmacology Authors: Takahashi Tsuyoshi, Tatsuyuki Ohtsuka, Yasuhiro Uno, Masahiro Utoh, Hiroshi Yamazaki, Toshiyuki Kume Tags: Original Paper Source Type: research

Caco ‐2 cells – expression, regulation and function of drug transporters compared with human jejunal tissue
ConclusionDifferences in transporter expression in Caco‐2 cells compared with jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under‐ or overestimation of certain transporters. The Caco‐2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. Copyright © 2016 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 4, 2016 Category: Drugs & Pharmacology Authors: S. Br ück, J. Strohmeier, D. Busch, M. Drozdzik, S. Oswald Tags: Special Issue Article Source Type: research

Effects of poloxamer 407 ‐induced hyperlipidemia on hepatic multidrug resistance protein 2 (Mrp2/Abcc2) and the pharmacokinetics of mycophenolic acid in rats
Abstract Hepatic multidrug resistance‐associated protein 2 (Mrp2) is responsible for the majority of the biliary elimination of endogenous and exogenous substances, therefore it is important to evaluate possible functional changes in Mrp2 activity under conditions of hyperlipidemia (HL). Thus, the present study assessed the protein expression and transporting activity of hepatic Mrp2 based on the in vivo biliary excretion of phenolsulfonphthalein (PSP) as a model anionic substrate for Mrp2 in poloxamer 407‐induced hyperlipidemic rats (HL rats) and compared these values with those for control rats. The pharmacokinetics ...
Source: Biopharmaceutics and Drug Disposition - September 3, 2016 Category: Drugs & Pharmacology Authors: Mi Hye Kwon, Ji Na Yoon, Yu Jin Baek, Yu Chul Kim, Yong Yeon Cho, Hee Eun Kang Tags: Original Paper Source Type: research

Issue Information ‐ JIP
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 3, 2016 Category: Drugs & Pharmacology Tags: Issue Information ‐ JIP Source Type: research

Issue Information ‐ TOC
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - September 3, 2016 Category: Drugs & Pharmacology Tags: Issue Information ‐ TOC Source Type: research

Atazanavir increases the plasma concentrations of 1200  mg raltegravir dose
ABSTRACT Raltegravir is a human immunodeficiency virus (HIV)‐1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice‐daily (BID). Raltegravir 1200 mg once‐daily (QD) [investigational QD formulation of 2 x 600 mg tablets; QD RAL] was found to be generally well tolerated and non‐inferior to the marketed 400 mg BID dose at 48 weeks in a Phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1‐mediated glucuronidation pathway, coadministration of UGT1A1 inhibitors may increase plasma levels of QD RAL. To assess...
Source: Biopharmaceutics and Drug Disposition - August 31, 2016 Category: Drugs & Pharmacology Authors: Rajesh Krishna, Lilly East, Patrick Larson, Chandni Valiathan, Kathleen Deschamps, Julie Ann Luk, Crystal Bethel ‐Brown, Helen Manthos, John Brejda, Michael Gartner Tags: Original Paper Source Type: research

Down ‐regulation of hepatic CYP3A1 expression in a rat model of indomethacin‐induced small intestinal ulcers
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - August 31, 2016 Category: Drugs & Pharmacology Authors: Shoji Kawauchi, Tsutomu Nakamura, Sayo Horibe, Toshihito Tanahashi, Shigeto Mizuno, Tsuneo Hamaguchi, Yoshiyuki Rikitake Tags: Original Paper Source Type: research

Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats
In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determinated by HPLC. Western blotting and real‐time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7‐day repeated administration, the plasma concentrations of metformin in the co‐administration group were significantly decreased compared to that in the metformin group. However, the parameter V/F of metformin in the co‐administration group was markedly increased compared to that in the metformin group. The hepatic,...
Source: Biopharmaceutics and Drug Disposition - August 31, 2016 Category: Drugs & Pharmacology Authors: Yan ‐rong Ma, A‐xi Shi, Hong‐yan Qin, Tiffany Zhang, Yan‐fang Wu, Guo‐qiang Zhang, Xin‐an Wu Tags: Original Paper Source Type: research

Physiologically based pharmacokinetic –pharmacodynamic modeling to predict concentrations and actions of sodium‐dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - August 31, 2016 Category: Drugs & Pharmacology Authors: Kazumi Mori, Ryuta Saito, Yoshinobu Nakamaru, Makiko Shimizu, Hiroshi Yamazaki Tags: Original Paper Source Type: research

Involvement of a proton ‐coupled organic cation antiporter in the blood–brain barrier transport of amantadine
Abstract The blood‐to‐brain transport of amantadine, a weak N‐methyl‐d‐aspartate (NMDA) antagonist, has been shown previously to participate in the cationic drug‐sensitive transport system across the mouse blood–brain barrier (BBB). The purpose of the present study was to characterize the influx transport system by means of both an in situ mouse brain perfusion technique and in vitro studies using rat immortalized brain capillary endothelial cells (GPNT). The observed concentration‐dependent initial uptake rate of [3H]amantadine suggested the involvement of a carrier‐mediated transport mechanism. The norm...
Source: Biopharmaceutics and Drug Disposition - August 23, 2016 Category: Drugs & Pharmacology Authors: Toyofumi Suzuki, Takahiko Aoyama, Naoto Suzuki, Masaru Kobayashi, Toshiro Fukami, Yoshiaki Matsumoto, Kazuo Tomono Tags: Original Paper Source Type: research

The effects of the concentration ‐dependent erythrocyte distribution of TAK‐802, a potent acetylcholinesterase inhibitor, on rat pharmacokinetics
Abstract The purpose of this study was to investigate the effect of the concentration‐dependent erythrocyte distribution of TAK‐802, a potent acetylcholinesterase inhibitor, on rat pharmacokinetics. In an ascending oral dose study, the maximum plasma concentration (Cmax) of TAK‐802 increased in a dose‐dependent manner. The time to reach Cmax decreased as the dose increased, whereas the total clearance was independent of the tested dose range. In this intravenous (i.v.) ascending dose study in rats, the apparent distribution volumes at steady state decreased, and the apparent terminal elimination rate constants incr...
Source: Biopharmaceutics and Drug Disposition - August 23, 2016 Category: Drugs & Pharmacology Authors: Masaaki Kakehi, Yoshihiko Tagawa, Akihiko Goto, Takahiro Kondo, Satoru Asahi Tags: Original Paper Source Type: research

Caco ‐2 Cells – Expression, Regulation and Function of Drug Transporters Compared To Human Jejunal Tissue
ConclusionDifferences in transporter expression in Caco‐2 cells compared to jejunal tissue, as well as expression dependence on culture time must be considered in in vitro studies to avoid under‐ or overestimation of certain transporters. The Caco‐2 cell model is not suitable for the evaluation of DDIs caused by transporter induction. This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - August 11, 2016 Category: Drugs & Pharmacology Authors: S Brueck, J Strohmeier, D Busch, M Drozdzik, S Oswald Tags: Special Issue Article Source Type: research

Characterization of loxoprofen transport in Caco ‐2 cells: the involvement of a proton‐dependent transport system in the intestinal transport of loxoprofen
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - August 11, 2016 Category: Drugs & Pharmacology Authors: Katsuya Narumi, Masaki Kobayashi, Ayuko Kondo, Ayako Furugen, Takehiro Yamada, Natsuko Takahashi, Ken Iseki Tags: Original Paper Source Type: research

Long ‐term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drug metabolism compared with Petri cultures
Abstract Human primary hepatocytes were cultivated in a microfluidic bioreactor and in Petri dishes for 13 days. mRNA kinetics in biochips showed an increase in the levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6, HNF4a, SULT1A1, UGT1A1 mRNA related genes when compared with post extraction levels. In addition, comparison with Petri dishes showed higher levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6 related genes at the end of culture. Functional assays illustrated a higher urea and albumin production over the period of culture in biochips. Bioreactor drug metabolism (midazolam and phenacetin) was not...
Source: Biopharmaceutics and Drug Disposition - July 19, 2016 Category: Drugs & Pharmacology Authors: Rachid Jellali, Thibault Bricks, S ébastien Jacques, Marie‐José Fleury, Patrick Paullier, Franck Merlier, Eric Leclerc Tags: Original Paper Source Type: research