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A quantitative threshold for high/low extent of urinary excretion of compounds in humans
In conclusion, 16.8% is a quantitative threshold value to distinguish between high and low UE and new molecular entities with cLogP and ACD labs cLogP values of ≤0.7 and ≥1.0 and ACD labs cLogD(pH=7.4) values of ≤0.0 and ≥0.5 could be identified as exhibiting high and low UE, respectively. Copyright © 2016 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - July 19, 2016 Category: Drugs & Pharmacology Authors: Rutwij A. Dave, Marilyn E. Morris 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, Sébastien Jacques, Marie‐José Fleury, Patrick Paullier, Franck Merlier, Eric Leclerc 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 - July 19, 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 - July 19, 2016 Category: Drugs & Pharmacology Tags: Issue Information ‐ TOC Source Type: research

TKI Combination Therapy: Strategy to Enhance Dasatinib Uptake through 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 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 limited...
Source: Biopharmaceutics and Drug Disposition - July 14, 2016 Category: Drugs & Pharmacology Authors: Ronilda D'Cunha, Sohyun Bae, Daryl J Murry, Guohua An Tags: Original Paper Source Type: research

In vivo individual variations in pharmacokinetics of efavirenz in cynomolgus monkeys genotyped for cytochrome P450 2C9
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - July 14, 2016 Category: Drugs & Pharmacology Authors: Kazuhide Iwasaki, Yusuke Kitsugi, Kanami Ikeda, Takahiro Yoshikawa, Shinya Hosaka, Shotaro Uehara, Yasuhiro Uno, Masahiro Utoh, Hiroshi Yamazaki Tags: Short Communication Source Type: research

In Vivo Use of the CYP Inhibitor 1 ‐Aminobenzotriazole to Increase Long‐term Exposure in Mice
In this study, we demonstrated a suitable dosing vehicle of ABT for continuous administration and increased exposure of antipyrine, which is a nonspecific probe of CYP, using ABT for a long period in mice. The dosing vehicle of ABT was the 0.5% (w/v) hydroxypropyl methylcellulose and 0.5% (v/v) Tween 80 in N,N‐Dimethylacetamide/20% hydroxypropyl‐β‐cyclodextrin aqueous solution (2:8, v/v) based on the duration of apparent solubility. After implantation of an ALZET osmotic pump with ABT, the plasma concentrations of ABT were maintained at more than 4.1 µg/mL over 336 h. Compared to the vehicle group, CLtot of ant...
Source: Biopharmaceutics and Drug Disposition - July 4, 2016 Category: Drugs & Pharmacology Authors: Ayahisa Watanabe, Kei Mayumi, Kyohei Nishimura, Hiromi Osaki Tags: Short Communication Source Type: research

The Pharmacokinetics of Propofol in ICU Patients Undergoing Long ‐Term Sedation
Abstract The aim of this study was to characterize the pharmacokinetics (PK) of propofol in ICU patients undergoing long‐term sedation and to assess the influence of routinely collected covariates on the PK parameters. Propofol concentration‐time profiles were collected from 29 patients. Non‐linear mixed‐effects modelling in NONMEM 7.2 was used to analyze the observed data. The propofol pharmacokinetics was best described with a three‐compartment disposition model. Non‐parametric bootstrap and visual predictive check were used to evaluate the adequacy of the developed model to describe the observations. The typ...
Source: Biopharmaceutics and Drug Disposition - June 30, 2016 Category: Drugs & Pharmacology Authors: Piotr Smuszkiewicz, Pawe ł Wiczling, Krzysztof Przybyłowski, Agnieszka Borsuk, Iwona Trojanowska, Marta Paterska, Jan Matysiak, Zenon Kokot, Edmund Grześkowiak, Agnieszka Bienert Tags: Original Paper Source Type: research

Cyp3a11 ‐mediated testosterone‐6β‐hydroxylation decreased, while UGT1a9‐mediated propofol O‐glucuronidation increased in mice with diabetes mellitus
This study was designed to investigate the alterations of major hepatic cytochrome P450s and UDP‐glucuronyltransferase enzymes in db/db mice. Mouse liver microsomes (MLMs) were obtained from male db/db mice and their wild type littermates. After incubation of the substrates separately with MLMs, the samples were pooled and analyzed by high‐throughput liquid chromatography‐tandem mass spectrometry system for the simultaneous study of 9 phase I metabolic reactions and 3 glucuronidation conjugation reactions to determine the activity of the metabolic enzymes. Compared with normal controls, Clint estimate for testosteron...
Source: Biopharmaceutics and Drug Disposition - June 30, 2016 Category: Drugs & Pharmacology Authors: Rong Shi, Jiasheng Wu, Cong Meng, Bingliang Ma, Tianming Wang, Yuanyuan Li, Yueming Ma Tags: Original Paper Source Type: research

Effect of hesperidins on the pharmacokinetics of CPT ‐11 and its active metabolite SN‐38 by regulating hepatic Mrp2 in rats
This study examined the effect of hesperidins on pharmacokinetics of CPT‐11 and SN‐38 as well as the regulatory effect on hepatic expression of Mrp2. Comparing to the control group, the AUC5‐t was increased to 115% of CPT‐11 and 122% of SN‐38; the CL was decreased to 87% for CPT‐11; the tissue concentration was increased in the liver, kidney and colon; and the accumulated biliary excretion was significantly decreased to 77% for CPT‐11 and 76% for SN‐38 in hesperidins‐treated rats. Furthermore, the expression of Mrp2 in liver was significantly decreased to 37% in hesperidins‐treated rats when compared to...
Source: Biopharmaceutics and Drug Disposition - June 30, 2016 Category: Drugs & Pharmacology Authors: Xingdong Wang, Zhi Rao, Hongyan Qin, Guoqiang Zhang, Yanrong Ma, Yongwen Jin, Miao Han, Axi Shi, Yanping Wang, Xinan Wu Tags: Original Paper Source Type: research

Factor VIII associated with lipidic nanoparticles retains efficacy in the presence of anti ‐Factor VIII antibodies in Hemophilia A mice
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 30, 2016 Category: Drugs & Pharmacology Authors: Krithika A. Shetty, Matthew P. Kosloski, Donald E. Mager, Sathy V. Balu ‐Iyer Tags: Original Paper Source Type: research

Simultaneous evaluation of substrate ‐dependent CYP3A inhibition using a CYP3A probe substrates cocktail
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 19, 2016 Category: Drugs & Pharmacology Authors: Eunyoung Lee, Jong Cheol Shon, Kwang ‐Hyeon Liu Tags: Short Communication Source Type: research

Effects of Poloxamer 407 ‐induced hyperlipidemi a on hepatic multidrug resistance protein 2 (Mrp2/Abcc2) and the pharmacokinetics of mycophenolic acid in rats
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - May 30, 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

In silico evaluation of warfarin–bucolome therapy
In conclusion, the concomitant administration of bucolome might not be useful for reducing the inter‐patient variation of (S)‐warfarin pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - May 22, 2016 Category: Drugs & Pharmacology Authors: Hisakazu Ohtani, Ryoko Hakoda, Ayuko Imaoka, Takeshi Akiyoshi Tags: Original Paper Source Type: research

Metabolic profiling of a novel antithrombotic compound, S002‐333 and enantiomers: metabolic stability, species comparison and in vitro–in vivo extrapolation
ConclusionThe in vitro CLint values for S002‐333, S004‐1032 and S007‐1558 were 0.027 ± 0.005, 0.025 ± 0.004 and 0.036 ± 0.005 ml/min/mg, respectively, in PHLM, indicating that S007‐1558 was the most metabolically unstable of the three. The LM of other species showed similar results. A common surrogate species to humans for S002‐333 and enantiomers was predicted as rabbit where the extrapolated hepatic clearance (CLH) did not show a significant difference to the in vivo CLH values. However, none of the species closely mimic humans with respect to the proportion of major metabolites (M‐1–M‐4)...
Source: Biopharmaceutics and Drug Disposition - May 22, 2016 Category: Drugs & Pharmacology Authors: Amrita Saxena, Guru R. Valicherla, Girish K. Jain, Rabi S. Bhatta, Anil K. Saxena, Jiaur R. Gayen Tags: Original Paper Source Type: research