Miura Masatomo, Kagaya Hideaki, Tada Hitoshi, Uno Tsukasa, Yasui-Furukori Norio, Tateishi Tomonori, Suzuki Toshio
Department of Pharmacy, Akita University Hospital, Akita, Japan.
Br J Clin Pharmacol. 2006 Mar;61(3):315-20. doi: 10.1111/j.1365-2125.2005.02566.x.
Rabeprazole is metabolized to some extent by CYP2C19. The purpose of this study was to elucidate the pharmacokinetics of each rabeprazole enantiomer in three different CYP2C19 genotype groups.
Twenty-four healthy subjects, of whom each each were homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs) and poor metabolizers (PMs) for CYP2C19, participated in our study. After a single oral dose of 20 mg of racemic rabeprazole, the plasma concentrations of the rabeprazole enantiomers were measured over the course of 24 h.
The area under the plasma concentration-time curves (AUC) of (R)-rabeprazole in homEMs, hetEMs and PMs were 1.8-, 2.2- and 2.4-fold, respectively, greater than those of (S)-rabeprazole; the relative AUC ratios of (R)- and (S)-rabeprazole in homEMs, hetEMs and PMs were 1:1.1:2.1 and 1:0.9:1.5, respectively. The mean maximum plasma concentrations (Cmax) of (R)-rabeprazole in homEMs, hetEMs and PMs were 1.7-, 1.9- and 1.8-fold higher, respectively, than those of the corresponding (S)-enantiomer (P<0.05). There was no difference between homEMs and PMs in the elimination half-life of (S)-rabeprazole, whereas the elimination half-life of (R)-rabeprazole was significantly longer in PMs than in homEMs [1.7 h (1.4, 2.0) (mean (95% confidence interval)]vs. 0.8 h (0.6, 1.0), respectively, P<0.0001).
(R)-Rabeprazole disposition was influenced to a greater degree by CYP2C19 genetic polymorphisms than was that of (S)-rabeprazole. The effect of CYP2C19 polymorphisms on the stereoselective disposition of rabeprazole was less than those of lansoprazole and omeprazole.
雷贝拉唑在一定程度上由CYP2C19代谢。本研究的目的是阐明雷贝拉唑各对映体在三种不同CYP2C19基因型组中的药代动力学。
24名健康受试者参与了我们的研究，其中分别为CYP2C19的纯合子广泛代谢者（homEMs）、杂合子广泛代谢者（hetEMs）和慢代谢者（PMs）。单次口服20mg消旋雷贝拉唑后，在24小时内测定雷贝拉唑对映体的血浆浓度。
（R）-雷贝拉唑在homEMs、hetEMs和PMs中的血浆浓度-时间曲线下面积（AUC）分别比（S）-雷贝拉唑大1.8倍、2.2倍和2.4倍；（R）-和（S）-雷贝拉唑在homEMs、hetEMs和PMs中的相对AUC比值分别为1:1.1:2.1和1:0.9:1.5。（R）-雷贝拉唑在homEMs、hetEMs和PMs中的平均最大血浆浓度（Cmax）分别比相应的（S）-对映体高1.7倍、1.9倍和1.8倍（P<0.05）。（S）-雷贝拉唑在homEMs和PMs中的消除半衰期无差异，而（R）-雷贝拉唑在PMs中的消除半衰期明显长于homEMs[分别为1.7小时（1.4，2.0）（均值（95%置信区间）]对0.8小时（0.6，1.0），P<0.0001）。
与（S）-雷贝拉唑相比，（R）-雷贝拉唑的处置受CYP2C19基因多态性的影响更大。CYP2C19多态性对雷贝拉唑立体选择性处置的影响小于兰索拉唑和奥美拉唑。
