Biopharmaceutics and Drug Disposition 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Inhibitory effects of sulfonylureas and non ‐steroidal anti‐inflammatory drugs on in vitro metabolism of canagliflozin in human liver microsomes
The objective of the present study was to evaluate the possible inhibitory effect of sulfonylureas and non‐steroidal anti‐inflammatory drugs (NSAIDs) on canagliflozin metabolism in vitro. Three sulfonylurea derivatives were evaluated as inhibitors: chlorpropamide, glimepiride and gliclazide. Two other NSAIDs were used as positive control inhibitors: niflumic acid and diclofenac. The rate of formation of canagliflozin metabolites was determined by HPLC analysis of in vitro incubations of canagliflozin as a substrate with and without inhibitors, using human liver microsomes (HLMs). Among sulfonylureas, glimepiride showed...
Source: Biopharmaceutics and Drug Disposition - February 22, 2018 Category: Drugs & Pharmacology Authors: Sara Algeelani, Dalal Alkhelb, David J. Greenblatt Tags: ORIGINAL PAPER Source Type: research
An iminium ion metabolite hampers the production of the pharmacologically active metabolite of a multikinase inhibitor KW ‐2449 in primates: irreversible inhibition of aldehyde oxidase and covalent binding with endogenous proteins
Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 164-174, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 16, 2018 Category: Drugs & Pharmacology Source Type: research
Verification of a physiologically based pharmacokinetic model of ritonavir to estimate drug –drug interaction potential of CYP3A4 substrates
Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 152-163, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 16, 2018 Category: Drugs & Pharmacology Source Type: research
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Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 164-174, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 16, 2018 Category: Drugs & Pharmacology Source Type: research
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Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 152-163, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 16, 2018 Category: Drugs & Pharmacology Source Type: research
Verification of a physiologically ‐based pharmacokinetic model of ritonavir to estimate drug‐drug interaction potential of CYP3A4 substrates
In this study, four physiologically‐based pharmacokinetic (PBPK) models of ritonavir as an in vivo time‐dependent inhibitor of CYP3A4 were created and verified for the oral doses of 20, 50, 100 and 200 mg using fraction absorbed (Fa) and oral clearance (CLoral) values reported in the literature, as transporter and CYP enzyme reaction phenotyping data were not available. The models were used subsequently to predict and compare the magnitude of AUC increase in nine reference DDI studies evaluating the effect of ritonavir at steady‐state on midazolam (CYP3A4 substrate) exposure. Midazolam AUC and Cmax ratios were predic...
Source: Biopharmaceutics and Drug Disposition - February 16, 2018 Category: Drugs & Pharmacology Authors: Ken ‐ichi Umehara, Felix Huth, Christina S. Won, Tycho Heimbach, Handan He Tags: ORIGINAL PAPER Source Type: research
Cytochrome P450 2C9 ‐natural antiarthritic interactions: evaluation of inhibition magnitude and prediction from in vitro data
This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed‐type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Rhein demonstrated the same ...
Source: Biopharmaceutics and Drug Disposition - February 1, 2018 Category: Drugs & Pharmacology Authors: Boon Hooi Tan, Nafees Ahemad, Yan Pan, Uma Devi Palanisamy, Iekhsan Othman, Beow Chin Yiap, Chin Eng Ong Tags: ORIGINAL PAPER Source Type: research
Differences in nonclinical pharmacokinetics between species and prediction of human pharmacokinetics of TAK ‐272 (SCO‐272), a novel orally active renin inhibitor
This report describes the selection of TAK‐272 (SCO‐272), a novel orally active renin inhibitor, as a clinical candidate via the detailed investigation of nonclinical PK data and human PK prediction.
The bioavailability (BA) of TAK‐272 after oral administration to rats and monkeys was low, especially in fasted monkeys, and the systemic exposure of TAK‐272 was highly variable in monkeys. The results of mass balance studies in animals suggested that the absorbed TAK‐272 was largely eliminated by metabolism. In vitro studies revealed that TAK‐272 was mainly metabolized by CYP3A4/5 in humans, and it was a P‐glyco...
Source: Biopharmaceutics and Drug Disposition - February 1, 2018 Category: Drugs & Pharmacology Authors: Takuya Ebihara, Mitsuhiro Nishihara, Junzo Takahashi, Fumihiro Jinno, Yoshihiko Tagawa Tags: ORIGINAL PAPER Source Type: research
Evaluation of the Metabolic Capability of Primary Human Hepatocytes in Three ‐dimensional Cultures on Microstructural Plates
Abstract
The NanoCulture Plate (NCP) is a novel microstructural plate designed as a base for the three‐dimensional culture of cells/tissues. Here, we examined whether or not the metabolic capability of human primary hepatocytes is well maintained during culture on NCPs. The hepatocytes formed aggregates after seeding and their ATP content was well maintained during culture for 21 days. Expression of CYP1A2, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 mRNAs was detected throughout the 21‐day culture period. Addition of CYP substrate drugs (midazolam, diclofenac, lamotrigine and acetaminophen) resulted in the formation of multiple ...
Source: Biopharmaceutics and Drug Disposition - February 1, 2018 Category: Drugs & Pharmacology Authors: Satoshi Koyama, Hiroshi Arakawa, Manabu Itoh, Norio Masuda, Kentaro Yano, Hajime Kojima, Takuo Ogihara Tags: ORIGINAL PAPER Source Type: research
An iminium ion metabolite hampers the production of the pharmacologically active metabolite of a multikinase inhibitor KW ‐2449 in primates: Irreversible inhibition of aldehyde oxidase and covalent binding with endogenous proteins
Abstract
We previously reported that KW‐2449, (E)‐1‐{4‐[2‐(1H‐Indazol‐3‐yl)vinyl]benzoyl}piperazine, a novel multikinase inhibitor developed for the treatment of leukemia patients, was oxidized to an iminium ion intermediate by monoamine oxidase B (MAO‐B) and then converted to its oxo‐piperazine form (M1) by aldehyde oxidase (AO). However, we found that the significant decrease in the pharmacologically active metabolite M1 following repeated administration of KW‐2449 in primates might hamper the effectiveness of the drug. We investigated the mechanism underlying this phenomenon and found that the AO a...
Source: Biopharmaceutics and Drug Disposition - February 1, 2018 Category: Drugs & Pharmacology Authors: Jun Hosogi, Rui Ohashi, Hiroshi Maeda, Kazuhiro Fujita, Junko Ushiki, Takashi Kuwabara, Yorihiro Yamamoto, Toru Imamura 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 - February 1, 2018 Category: Drugs & Pharmacology Tags: ISSUE INFORMATION Source Type: research
Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for its CYP3A and CYP2D inhibition in rat liver microsomes
Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 143-151, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - January 12, 2018 Category: Drugs & Pharmacology Source Type: research
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Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 143-151, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - January 12, 2018 Category: Drugs & Pharmacology Source Type: research
Inhibitory effects of sulfonylureas and non ‐steroidal anti‐inflammatory drugs on in vitro metabolism of canagliflozin in human liver microsomes
Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 135-142, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - January 10, 2018 Category: Drugs & Pharmacology Source Type: research
Application of a physiologically ‐based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate
Biopharmaceutics&Drug Disposition,Volume 39, Issue 3, Page 125-134, March 2018. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - January 10, 2018 Category: Drugs & Pharmacology Source Type: research
