CYP2C19 genotype and the PPIs--focus on rabeprazole.. P W Y Lim; K L Goh; B C Y Wong (2005) Journal of gastroenterology and hepatology display abstract
Amongst all the proton pump inhibitors (PPI), the hepatic metabolism of rabeprazole is least dependent on the CYP4502C19 system. Rabeprazole is therefore the PPI least affected by CYP4502C19 genetic polymorphism. This unique feature of rabeprazole complements rabeprazole's fast onset of action, and may lead to profound and consistent inhibition of gastric acid secretion in the treatment of acid-related disorders.
Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes.. Mikiko Shimizu; Tsukasa Uno; Norio Yasui-Furukori; Kazunobu Sugawara; Tomonori Tateishi (2006) European journal of clinical pharmacology display abstract
OBJECTIVE: Rabeprazole as a proton pump inhibitor (PPI) is mainly reduced to rabeprazole thioether via a nonenzymatic pathway, with minor CYP2C19 and CYP3A4 involvement. The aim of this study was to compare possible effects of clarithromycin and verapamil as inhibitors of CYP3A4 on the pharmacokinetics of rabeprazole among CYP2C19 genotypes. METHODS: A three-way randomized, double-blind, placebo-controlled crossover study was performed. Nineteen volunteers, of whom six were homozygous extensive metabolizers (EMs), eight were heterozygous EMs, and five were poor metabolizers (PMs) for CYP2C19, received three 6-day courses of either daily 800 mg clarithromycin, 240 mg verapamil, or placebo in a randomized fashion, with a single oral dose of 20 mg rabeprazole on day 6 in all cases. Plasma concentrations of rabeprazole and rabeprazole thioether were monitored up to 24 h after the dosing. RESULTS: In the control phase, the AUC(0-infinity) values for rabeprazole and rabeprazole thioether were 1,005+/-366 and 412+/-149 ng.h/ml in homozygous EMs, 1,108+/-340 and 491+/-245 ng.h/ml in heterozygous EMs, and 2,697+/-364 and 2,116+/-373 ng.h/ml in PMs, respectively. There were significant differences (p
Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration-time curve.. Takenori Niioka; Tsukasa Uno; Norio Yasui-Furukori; Mikiko Shimizu; Kazunobu Sugawara; Tomonori Tateishi (2006) European journal of clinical pharmacology display abstract
OBJECTIVE: The purpose of this study is to evaluate whether a simple formula using limited blood samples can predict the area under the plasma rabeprazole concentration-time curve (AUC) in co-administration with CYP inhibitors. METHODS: A randomized double-blind placebo-controlled crossover study design in three phases was conducted at intervals of 2 weeks. Twenty-one healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single oral 20-mg dose of rabeprazole after three 6-day pretreatments, i.e., clarithromycin 800 mg/day, fluvoxamine 50 mg/day, and placebo. Prediction formulas of the AUC were derived from pharmacokinetics data of 21 subjects in three phases using multiple linear regression analysis. Ten blood samples were collected over 24 h to calculate AUC. Plasma concentrations of rabeprazole was measured by an HPLC-assay (l.l.q.=1 ng/ml). RESULTS: The AUC was based on all the data sets (n=63). The linear regression using two points (C3 and C6) could predict AUC(0-infinity) precisely, irrespective of CYP2C19 genotypes and CYP inhibitors (AUC(0-infinity)=1.39xC3+7.17xC6+344.14, r (2)=0.825, p