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Functional characterization and tissue expression of marmoset cytochrome P450 2E1
In this study, the full‐length cDNA encoding P450 2E1 enzyme was isolated from marmoset livers by reverse transcription (RT)‐polymerase chain reaction (PCR). Marmoset P450 2E1 amino acid sequences were highly identical (>88%) to those of cynomolgus monkey and human P450 2E1 enzymes. Phylogenetic analysis indicated a close evolutionary relationship among marmoset, cynomolgus monkey, and human P450 2E1 enzymes. The tissue expression pattern analyzed by real‐time RT PCR and immunoblotting demonstrated that marmoset P450 2E1 mRNA and proteins were predominantly expressed in livers. Marmoset P450 2E1 enzyme heterologou...
Source: Biopharmaceutics and Drug Disposition - May 5, 2017 Category: Drugs & Pharmacology Authors: Shotaro Uehara, Yasuhiro Uno, Etsuko Tomioka, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki Tags: SHORT COMMUNICATION Source Type: research

Issue Information
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - May 2, 2017 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

SGK1/Nedd4 ‐2 signaling pathway regulates the activity of Human Organic Anion Transporters 3
Abstract Human organic anion transporter 3 (hOAT3) is localized at the basolateral membrane of renal proximal tubule cells and facilitates renal secretion of numerous clinical drugs, including anti‐HIV therapeutics, anti‐tumor drugs, antibiotics, antihypertension drugs, and anti‐inflammatories. In the present study, we explored the role of serum and glucocorticoid‐inducible kinase 1 (sgk1) in the regulation of hOAT3. We showed that over‐expression of sgk1 in hOAT3‐expressing cells stimulated hOAT3 transport activity by enhancing the transporter expression at the plasma membrane, kinetically reflected as an incr...
Source: Biopharmaceutics and Drug Disposition - May 1, 2017 Category: Drugs & Pharmacology Authors: Haoxun Wang, Guofeng You Tags: ORIGINAL PAPER Source Type: research

In vitro evaluation of potential transporter ‐mediated drug interactions of evogliptin
The objective of this study was to evaluate the DDI potential of evogliptin using various in vitro assays in transporter‐expressing cell lines. After incubating evogliptin with cells overexpressing OAT1, OAT3, OCT2, OATP1B1, and OATP1B3, there was no notable cellular accumulation of evogliptin (fold accumulation, 0.41–1.86). In bidirectional transport assays using Caco‐2 cell monolayer, a high efflux ratio (ER, 522) of evogliptin was observed, which was significantly decreased (97.96%) in the presence of a potent P‐gp inhibitor. In assays using MDCKII‐BCRP cell monolayers, by contrast, a low net ER (1.16‐1.26) ...
Source: Biopharmaceutics and Drug Disposition - May 1, 2017 Category: Drugs & Pharmacology Authors: Dae Y. Lee, Hye W. Chae, Hyunjoo Shim Tags: SHORT COMMUNICATION Source Type: research

Application of Physiologically ‐Based Pharmacokinetic Modeling to Predict Drug Disposition in Pregnant Populations
ABSTRACT Pregnancy is associated with numerous physiologic changes that influence absorption, distribution, metabolism and excretion. Moreover, the magnitude of these effects changes as pregnancy matures. For most medications, there is limited information available about changes in drug disposition that can occur in pregnant patients, yet most women are prescribed one or more medications during pregnancy. In this investigation, PBPK modeling was used to assess the impact of pregnancy on the pharmacokinetic profiles of three medications (metformin, tacrolimus, oseltamivir) using the Simcyp® Simulator. The Simcyp pregnancy...
Source: Biopharmaceutics and Drug Disposition - May 1, 2017 Category: Drugs & Pharmacology Authors: Vamshi Krishna Jogiraju, Suvarchala Avvari, Rakesh Gollen, David R. Taft Tags: ORIGINAL PAPER Source Type: research

Optimization 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 underestimation 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. In...
Source: Biopharmaceutics and Drug Disposition - April 18, 2017 Category: Drugs & Pharmacology Authors: Oliver J.D. Hatley, Christopher R. Jones, Aleksandra Galetin, Amin Rostami ‐Hodjegan Tags: Special Issue Article Source Type: research

Issue Information
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - April 18, 2017 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Inactivation kinetics and residual activity of CYP3A4 after treatment with erythromycin
In conclusion, relatively long‐term evaluation of the kinetics of CYP3A4 inactivation revealed that the enzyme was not fully inactivated by erythromycin. To improve the estimation of the extent of the drug‐drug interactions induced by MBI from in vitro data, longer‐term investigations of the target enzyme's inactivation profile might be necessary. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - April 1, 2017 Category: Drugs & Pharmacology Authors: Yuko Ishikawa, Takeshi Akiyoshi, Ayuko Imaoka, Hisakazu Ohtani Tags: ORIGINAL PAPER Source Type: research

Revisiting the role of gut wall in the fate of orally administered drugs: Why now and to what effect?
(Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - March 19, 2017 Category: Drugs & Pharmacology Authors: Amin Rostami ‐Hodjegan, Ikumi Tamai, K. Sandy Pang Tags: Editorial Commentary Source Type: research

Issue Information
No abstract is available for this article. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - March 19, 2017 Category: Drugs & Pharmacology Tags: Issue Information Source Type: research

Absorption, distribution and excretion of the anti ‐tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis
Abstract Delamanid (OPC‐67683, Deltyba™, nitro‐dihydro‐imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug‐resistant tuberculosis. The absorption, distribution and excretion of delamanid‐derived radioactivity were investigated after a single oral administration of 14C–delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 h post‐dose, and thereafter decreased slowly. Radioactivity levels were 3‐ to 5‐fold higher in lung tissue at time to maximum concentration compared with plasma. In addition,...
Source: Biopharmaceutics and Drug Disposition - March 7, 2017 Category: Drugs & Pharmacology Authors: Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara Tags: Original Paper Source Type: research

Development of a physiologically based pharmacokinetic model to predict the effects of Flavin ‐Containing Monooxygenase 3 (FMO3) polymorphisms on Itopride exposure
Abstract Itopride, a substrate of FMO3, has been used for the symptomatic treatment of various gastrointestinal disorders. Physiologically based pharmacokinetic (PBPK) modeling was applied to evaluate the impact of FMO3 polymorphism on itopride pharmacokinetics (PK). The Asian populations within the Simcyp simulator were updated to incorporate information on frequency, activity and abundance of FMO3 enzyme with different phenotypes. A meta‐analysis of relative enzyme activities suggested that FMO3 activity in subjects with homozygous Glu158Lys and Glu308Gly mutations (Lys158 and Gly308) in both alleles is ~47% lower than...
Source: Biopharmaceutics and Drug Disposition - March 2, 2017 Category: Drugs & Pharmacology Authors: Wangda Zhou, Helen Humphries, Sibylle Neuhoff, Iain Gardner, Eric Masson, Nidal Al ‐Huniti, Diansong Zhou Tags: SHORT COMMUNICATION Source Type: research

Prediction of liver volume – a population‐based approach to meta‐analysis of paediatric, adult and geriatric populations – an update
In conclusion, extension and re‐parameterization of the existing Johnson model adequately describes changes in liver volume using the body surface area in all investigated populations. Copyright © 2017 John Wiley & Sons, Ltd. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - March 1, 2017 Category: Drugs & Pharmacology Authors: Ben G. Small, Bernd Wendt, Masoud Jamei, Trevor N. Johnson Tags: Original Paper Source Type: research

Pharmacokinetic Analysis of Inhaled Salmeterol in Asthma Patients: Evidence from Two Dry Powder Inhalers
ABSTRACT Salmeterol (SAL) is a long‐acting β2‐adrenergic agonist, which is widely used in the asthma therapy. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled SAL in asthma patients using two different dry powder inhalers. This analysis was based on data from 45 subjects who participated in a two‐sequence, four period crossover bioequivalence (BE) study after single administration of the test (T) and reference (R) products. In order to mimic more closely the real treatment conditions, activated charcoal was not co‐administered. Plasma concentration (C) – time (t) data were initially ...
Source: Biopharmaceutics and Drug Disposition - March 1, 2017 Category: Drugs & Pharmacology Authors: Konstantina Soulele, Panos Macheras, Vangelis Karalis Tags: ORIGINAL PAPER Source Type: research

Pharmacokinetic interactions in mice between irinotecan and MBL ‐II‐141, an ABCG2 inhibitor
ConclusionsThese results may help to anticipate the pharmacokinetic interactions between MBL‐II‐141 and other ABCG2 substrates. The irinotecan‐MBL‐II‐141 interaction is also expected to occur in humans. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - February 15, 2017 Category: Drugs & Pharmacology Authors: Emilie H énin, Mylène Honorat, Jérôme Guitton, Attilio Di Pietro, Léa Payen, Michel Tod Tags: Original Paper Source Type: research