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Retracted: Physiologically based pharmacokinetic predictions of intestinal BCRP ‐mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans
The above article, published online on 06 February 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, K. Sandy Pang, and John Wiley & Sons, Ltd. The authors retracted the paper due to errors associated with use of log D vs. log P of telmisartan as inputs of the PBPK model. The authors concluded that there are too many changes in the article to be resolved by an Erratum, and had requested a retraction. ReferenceBae, S. H., Park, W. ‐S., Han, S., Park, G., Lee, J., Hong, T., Jeon, S., and Yim, D. ‐S. (2016) Physiologically based pha...
Source: Biopharmaceutics and Drug Disposition - February 6, 2017 Category: Drugs & Pharmacology Authors: Soo Hyeon Bae, Wan ‐Su Park, Seunghoon Han, Gab‐jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon, Dong‐Seok Yim Tags: Original Paper Source Type: research

Physiologically based pharmacokinetic predictions of intestinal BCRP ‐mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans
Abstract It was recently reported that the Cmax and AUC of rosuvastatin increases when it is co‐administered with telmisartan. The aim of this study was to explore the mechanism of the interaction of telmisartan and rosuvastatin. A full‐PBPK model of telmisartan was developed, and the rosuvastatin model in Simcyp (version 15)’s drug library was modified to reflect ethnic differences in rosuvastatin exposure. PK characteristics, including intestinal and hepatic transporter/enzyme specificities of telmisartan and rosuvastatin, were incorporated into the PBPK models to simulate a rosuvastatin (20 mg) – telmisartan (8...
Source: Biopharmaceutics and Drug Disposition - February 5, 2017 Category: Drugs & Pharmacology Authors: Soo Hyeon Bae, Wan ‐Su Park, Seunghoon Han, Gab‐jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon, Dong‐Seok Yim Tags: Original Paper Source Type: research

Physiologically based pharmacokinetic modeling revealed minimal codeine intestinal metabolism in first ‐pass removal in rats
Abstract The physiologically based model with segregated flow to the intestine (SFM‐PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe the first‐pass glucuronidation of morphine (M) to morphine‐3β‐glucuronide (MG) in rats after intraduodenal (i.d.) and intravenous (i.v.) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The segregated flow model (SFM) described a disproportionately greater extent of intestinal morphine glucuronidation for i.d. vs. i.v. administration. The prese...
Source: Biopharmaceutics and Drug Disposition - January 25, 2017 Category: Drugs & Pharmacology Authors: Keumhan Noh, Shu Chen, Qi J. Yang, K. Sandy Pang Tags: Original Paper Source Type: research

Issue Information
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - January 25, 2017 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Inhibitory effect of ezetimibe can be prevented by an administration interval of 4  h between α‐tocopherol and ezetimibe
This study investigated the influence of ezetimibe on the absorption of α‐tocopherol with single administration and long‐term administration. An approach to avoid its undesirable consequence was also examined. α‐Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of α‐tocopherol and tissue concentrations were investigated. The plasma concentration of α‐tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of α‐tocopherol was prevented by an a...
Source: Biopharmaceutics and Drug Disposition - January 19, 2017 Category: Drugs & Pharmacology Authors: Shunsuke Nashimoto, Yuki Sato, Yoh Takekuma, Mitsuru Sugawara Tags: Original Paper Source Type: research

Influence of the pharmacokinetic profile on the plasma glucose lowering effect of PPAR γ agonist pioglitazone in Wistar fatty rats
Abstract Although the mechanism of action for peroxisome proliferator‐activated receptor gamma (PPARγ) agonists has been extensively explored, the impact of the pharmacokinetic (PK) profile on the pharmacodynamic (PD) effects of PPARγ agonists has not been elucidated in detail. We evaluated the importance of the PK profile of PPARγ agonist for its PD effect based on population PK/PD analysis. Pioglitazone hydrochloride, the PPARγ agonist, was administered orally to Wistar fatty rats once a day (qd) or once every other day (q2d) as double the amount for the qd treatment. The plasma glucose lowering effect was selected...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Akihiko Goto, Yoshihiko Tagawa, Yoshiaki Kimura, Akifumi Kogame, Yuu Moriya, Nobuyuki Amano Tags: ORIGINAL PAPER Source Type: research

Impact of acute fat mobilization on the pharmacokinetics of the highly fat distributed compound TAK ‐357, investigated by physiologically‐based pharmacokinetic (PBPK) modeling and simulation.
Abstract In a dog toxicokinetic study, an unusual plasma concentration increase of the highly lipophilic compound TAK‐357 was observed 2‐weeks after termination of a 2‐week repeated dosing in one dog with acute body weight loss. The present study investigates the cause of this increase. A physiologically based pharmacokinetic (PBPK) model was constructed using the rat and dog pharmacokinetic data. Using the constructed model, the TAK‐357 concentration profile in case of body weight change was simulated. PBPK model‐derived simulation suggested that redistribution from adipose tissues to plasma due to loss of body ...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Akihiko Goto, Yoshihiko Tagawa, Yuu Moriya, Sho Sato, Yoshiyuki Furukawa, Takeshi Wakabayashi, Tetsuya Tsukamoto, Joost DeJongh, Tamara J. Steeg, Toshiya Moriwaki, Satoru Asahi Tags: ORIGINAL PAPER Source Type: research

Influence of vasomodulators and tumor transplantation on the disposition of 5 ‐fluorouracil after application to the liver surface in rats
This study investigated the effect of epinephrine (a vasoconstrictor) and hydralazine (a vasodilator) on the hepatic disposition of 5‐fluorouracil (5‐FU) after application to the liver surface in rats. Normal livers were compared with a Walker 256 carcinoma cell tumor model. A cylindrical diffusion cell was attached to the liver surface. 5‐FU was added into the diffusion cell in combination with vasomodulators or after pretreatment with epinephrine. After selected treatment times, 5‐FU concentrations were assayed at three sites in the excised livers. 5‐FU concentration in the region under the cell attachment site...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Yukinobu Kodama, Miyuki Horishita, Ayako Tokunaga, Hirotaka Miyamoto, Shintaro Fumoto, Hitoshi Sasaki, Junzo Nakamura, Koyo Nishida Tags: ORIGINAL PAPER Source Type: research

Application of the MechPeff Model to Predict Passive Effective Intestinal Permeability in the Different Regions of the Rodent Small Intestine and Colon
Abstract A major component of Physiologically‐Based Pharmacokinetic (PBPK) models is prediction of the rate and extent of absorption of orally dosed drugs for which knowledge of effective passive intestinal permeability (Peff) is essential. Single pass intestinal perfusion (SPIP) studies are used to establish effective permeability in vivo but are difficult to perform in rodents while mechanistic models to predict drug Peff in rat and mouse have not been published. This work evaluates the predictive performance of the ‘MechPeff’ model to predict Peff in the rodent intestine based upon knowledge of regional gut physio...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: D. Pade, M. Jamei, A. Rostami ‐Hodjegan, D.B. Turner Tags: Original Paper Source Type: research

Optimisation of intestinal microsomal preparation in the rat: A systematic approach to assess the influence of various methodologies on metabolic activity and scaling factors
Abstract The metabolic capacity of the intestine and its importance as the initial barrier to systemic exposure can lead to under‐estimation of first‐pass, and thus overestimation of oral bioavailability. However, the in vitro tools informing estimates of in vivo intestinal metabolism are limited by the complexity of the in vitro matrix preparation and uncertainty with the scaling factors for in vitro to in vivo extrapolation. A number of methods currently exist in the literature for the preparation of intestinal microsomes; however, the impact of key steps in the preparation procedure has not been critically assessed....
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Oliver J. D. Hatley, Christopher R. Jones, Aleksandra Galetin, Amin Rostami ‐Hodjegan Tags: Original Paper Source Type: research

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data
ABSTRACT Extensive gut metabolism is often associated with the risk of low and variable bioavailability. Prediction of the fraction of drug escaping gut wall metabolism as well as transporter‐mediated secretion (Fg) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate Fg, and based on the outcome to provide recommendations for the prediction of human Fg during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes ...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Estelle Yau, Carl Petersson, Hugues Dolgos, Sheila Annie Peters Tags: Special Issue Article Source Type: research

Pharmacokinetics and protein binding of MPT0B292
ABSTRACT MPT0B292 was identified through screening of compounds able to selectively acetylate α‐tubulins in cells and exhibited potent anti‐tumor, anti‐angiogenesis and anti‐metastatic effects in vitro and in vivo. Because of poor water solubility, MPT0B292 is difficult to formulate with conventional approaches and hence difficulties are experienced in research practices. We mixed MPT0B292 with albumin in the aqueous solvent to form drug albumin nanoparticles with the size range around 333 nm. We investigated unbound fractions of these nanoparticles in different or same albumin concentration solutions. Unlike mo...
Source: Biopharmaceutics and Drug Disposition - December 31, 2016 Category: Drugs & Pharmacology Authors: Yu ‐En Tien, Chan‐Jung Li, Jing‐Ping Liou, Jang‐Yang Chang, Jin‐ding Huang Tags: Original Paper Source Type: research

Inhibitory effect of ezetimibe can be prevented by an administration interval of 4  h between α‐tocopherol and ezetimibe
In this study, we investigated the influence of ezetimibe on the absorption of α‐tocopherol with single administration and long‐term administration. We also examined an approach to avoid its undesirable consequence. α‐Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of α‐tocopherol and tissue concentrations were investigated. The plasma concentration of α‐tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of α‐tocopherol was prevented...
Source: Biopharmaceutics and Drug Disposition - December 26, 2016 Category: Drugs & Pharmacology Authors: Shunsuke Nashimoto, Yuki Sato, Yoh Takekuma, Mitsuru Sugawara Tags: Original Paper Source Type: research

Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions
ABSTRACT The dissolution, intestinal absorption and presystemic metabolism of a drug depend on its physicochemical characteristics but also on numerous physiological (e.g. gastrointestinal pH, volume, transit time, morphology) and biochemical factors (e.g. luminal enzymes and flora, intestinal wall enzymes and transporters). Over the last decade, evidence has accumulated indicating that these factors may differ in children and adults resulting in age‐related changes in drug exposure and drug response. Thus, drug dosage may require adjustment for the pediatric population to ensure the desired therapeutic outcome and to av...
Source: Biopharmaceutics and Drug Disposition - December 14, 2016 Category: Drugs & Pharmacology Authors: Nicolas Jean ‐Marie, Bouzom François, Hugues Chanteux, Ungell Anna‐Lena Tags: Invited Review Source Type: research

Evaluation of drug efficacy of DPP ‐4 inhibitors based on theoretical analysis with pharmacokinetics and pharmacodynamics
This article is protected by copyright. All rights reserved. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - December 14, 2016 Category: Drugs & Pharmacology Authors: Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada Tags: Original Paper Source Type: research