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

Acetylshikonin is a Novel Non ‐selective Cytochrome P450 Inhibitor
Abstract Acetylshikonin is biologically active compound with anti‐cancer and anti‐inflammatory activity, which is isolated from the root of Lithospermum erythrorhizoma. We have recently discovered a inhibitory effect of acetylshikonin against CYP2J2 activity. Based on this result, we expanded our study to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μM. Pre‐incubation of acetylshik...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Jong Cheol Shon, Nguyen Minh Phuc, Won Cheol Kim, Jae Kyung Heo, Zhexue Wu, Hyunyoung Lee, Kwang ‐Hyeon Liu Tags: SHORT COMMUNICATION Source Type: research

Impact of enzalutamide and its main metabolite N ‐desmethyl enzalutamide on pharmacokinetically important drug metabolizing enzymes and drug transporters
Abstract Enzalutamide is a new drug against castration‐resistant prostate cancer. Recent data indicate profound induction of drug metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro data on other CYP enzymes, drug conjugating enzymes or drug transporters is scarce. Moreover, mechanisms of induction are poorly investigated and the effects of the active metabolite N‐desmethyl enzalutamide are unknown. Using LS180 cells as an induction model and quantitative real‐time reverse transcription polymerase chain reaction, our study demonstrated a concentration‐dependent induction of CY...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Johanna Weiss, Jutta Kocher, Corina Mueller, Stephanie Rosenzweig, Dirk Theile Tags: ORIGINAL PAPER Source Type: research

5 ‐Fluorouracil treatment alters the expression of intestinal transporters in rats
In conclusion, 5‐FU‐induced intestinal damage was shown to alter the expression of these transporters, especially in the upper intestinal segment, while the characteristics of the influence varied among the transporters. The 5‐FU‐induced intestinal damage may affect transporter‐mediated drug absorption of orally administered drugs in the clinical setting. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Keiichi Yotsumoto, Takeshi Akiyoshi, Naoki Wada, Ayuko Imaoka, Hisakazu Ohtani Tags: ORIGINAL PAPER Source Type: research

Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: evaluation of drug ‐drug interactions mediated by organic anion transporter 3
Abstract Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyze the potential drug‐drug interactions between MTX and gastric antisecretory drugs in high‐dose MTX (HD‐MTX) therapy. We retrospectively analyzed the impact of PPIs on the plasma MTX concentration on 73 cycles of HD‐MTX ther...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Katsuya Narumi, Yu Sato, Masaki Kobayashi, Ayako Furugen, Kumiko Kasashi, Takehiro Yamada, Takanori Teshima, Ken Iseki Tags: ORIGINAL PAPER Source Type: research

Metabolism of 7 ‐ethoxycoumarin, flavanone and steroids by cytochrome P450 2C9 variants
Abstract CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild‐type CYP2C9 and mutants were coexpressed with NADPH‐cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward 7‐ethoxycoumarin, flavanone and steroids were examined. Six CYP2C9 variants showed Soret peaks (450 nm) typical of P450 in reduced CO‐difference spectra. CYP2C9.38 had the highest 7‐ethoxycoumarin de‐ethylase activity. All the CYP2C9 variants showed lower flavanone 6‐hydroxylation activities than CYP2C9.1 (the wild‐typ...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Tomohide Uno, Ryosuke Nakano, Kengo Kanamaru, Shinji Takenaka, Yuichi Uno, Hiromasa Imaishi Tags: ORIGINAL PAPER Source Type: research

D ‐Malate decreases renal content of α‐ketoglutarate, a driving force of organic anion transporters OAT1 and OAT3, resulting in inhibited tubular secretion of phenolsulfonphthalein, in rats
In this study, we examined effects of D‐malate on the rat organic anion transport system. Uptake of 6‐carboxyfluorescein by HEK293 cells expressing rOAT1 or rOAT3 was not affected by D‐malate and L‐malate. Until 60 min after the intravenous injection of phenolsulfonphthalein (PSP), a typical substrate of the renal organic anion transporters, as a bolus to rats, 47.1% of the dose was recovered in the urine, and its renal clearance was estimated to be 8.60 ml/min/kg. D‐Malate but not L‐malate interfered with its renal excretion, resulting in the delayed elimination of PSP from plasma. No effect of D‐malate was ...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Yuichi Uwai, Tatsuya Kawasaki, Tomohiro Nabekura Tags: ORIGINAL PAPER Source Type: research

Pharmacokinetics of dinalbuphine sebacate and nalbuphine in Human after Intramuscular Injection of dinalbuphine sebacate in an Extended ‐Release Formulation
Abstract Nalbuphine is a semi‐synthetic opioid indicated for the relief of moderate to severe pain. Its short half‐life requires frequent injections in clinical practices, resulting in greater incidences of adverse events. We have developed a prodrug of nalbuphine, dinalbuphine sebacate (DNS), dissolved in a simple oil‐based injectable formulation, which could deliver and maintain effective blood nalbuphine level. An open‐label, prospective, two‐period study was performed in healthy volunteers to verify the extended blood concentration profile of nalbuphine. Twelve healthy Taiwanese were randomized to receive int...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Yu en Tien, Wen ‐Chuan Huang, Hui‐Yuan Kuo, Lily Tai, Yow‐Shieng Uang, Wendy H. Chern, Jin‐Ding Huang Tags: SHORT COMMUNICATION Source Type: research

The application of physiologically ‐based pharmacokinetic modelling to assess the impact of antiretroviral‐mediated drug‐drug interactions on piperaquine antimalarial therapy during pregnancy
This study applied mechanistic pharmacokinetic modelling to predict pharmacokinetics in non‐pregnant and pregnant patients, which was validated in distinct customised population groups from Thailand, Sudan and Papua New Guinea. In each population group, no significant difference in day 7 concentrations were observed during different gestational weeks (GW) (weeks 10‐40), supporting the notion that PQ is safe throughout pregnancy with consistent pharmacokinetics, although possible teratogenicity may limit this. Antiretroviral‐mediated DDIs (efavirenz and ritonavir) had moderate effects on PQ during different gestationa...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: Olusola Olafuyi, Michael Coleman, Raj K.S. Badhan Tags: ORIGINAL PAPER Source Type: research

Clinical assessment of the lag ‐time and tmax of pellets with controlled release of glucose: in‐vitro/in‐vivo comparison using 13C‐breath test
Abstract Maintaining a stable glycemia in diabetes mellitus type 1 requires flexible insulin application and carbohydrates intake to affected individuals. In real life, there might be some situations limiting the insulin‐sugar balance control, e.g. night sleep or prolonged sport activities. Glucose pellets with pre‐determined time lag between pellet administration and glucose release were developed to mimic "snack eaten in advance". In this article, 13C‐glucose breath test is introduced to translate the laboratory dissolution testing to clinical confirmation of the glucose release pattern using 5 per cent of δ abund...
Source: Biopharmaceutics and Drug Disposition - July 1, 2017 Category: Drugs & Pharmacology Authors: David Neumann, Jan Musel ík, Dana Sabadková, Sylvie Pavloková, Jana Špirková, Aleš Franc Tags: ORIGINAL PAPER Source Type: research

Letter to the Editor, Physiologically based pharmacokinetic predictions of intestinal BCRP ‐mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans
(Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 28, 2017 Category: Drugs & Pharmacology Authors: Ruben Kanter, Christopher Kohl Tags: LETTER TO THE EDITOR Source Type: research

Author's response to letter to the editor on: Physiologically based pharmacokinetic predictions of intestinal BCRP ‐mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans
(Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 28, 2017 Category: Drugs & Pharmacology Authors: Dong ‐Seok Yim Tags: COMMENTARY Source Type: research

Efavirenz clearances in vitro and in vivo in six cynomolgus monkeys associated with polymorphic cytochrome P450 2C9 and simulated by individual physiologically based pharmacokinetic models
This study provides important information to help simulate clearances of efavirenz and related medicines associated with polymorphic P450 2C9 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of liver microsomal clearance for estimating in vivo drug clearance with simplified PBPK modeling. (Source: Biopharmaceutics and Drug Disposition)
Source: Biopharmaceutics and Drug Disposition - June 13, 2017 Category: Drugs & Pharmacology Authors: Masahiro Utoh, Tomonori Miura, Takashi Kusama, Shotaro Uehara, Makiko Shimizu, Yasuhiro Uno, Hiroshi Yamazaki Tags: SHORT COMMUNICATION Source Type: research

Influence of the pharmacokinetic profile on the plasma glucose lowering effect of the 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. The importance of the PK profile of PPARγ agonist was evaluated 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 (q.d.) or once every other day (q.2d.) as double the amount for the q.d. treatment. The plasma glucose lowering effect was s...
Source: Biopharmaceutics and Drug Disposition - May 28, 2017 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 mobilisation 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 the case of body weight change was simulated. The PBPK model‐derived simulation suggested that redistribution from adipose tissues to plasma due to a loss...
Source: Biopharmaceutics and Drug Disposition - May 23, 2017 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