Open AccessEvaluation of the relationship between polymorphisms in CYP2C19 and the single‐dose pharmacokinetics of omeprazole in healthy Chinese volunteers: A multicenter study
Author(s) -
Zhou Shuang,
Xie Ran,
Zhang Xiaodan,
He Xu,
Huang Jie,
Jungang Yin,
Liao Man,
Ding Ying,
Yang Dandan,
Liu Ying,
Zhang Qian,
Yang Guoping,
Liu Fang,
Guan Shengjiang,
He Qing,
Lou Honggang,
Gong Fengyun,
Meng Xianmin,
Xiang Qian,
Zhao Xia,
Cui Yimin
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13255
Subject(s) - omeprazole , cyp2c19 , pharmacokinetics , medicine , pharmacology , multicenter study , randomized controlled trial , metabolism , cytochrome p450
The aim of this study was to evaluate the relationship between polymorphisms in CYP2C19 and the single‐dose pharmacokinetics (PKs) of omeprazole in healthy Chinese volunteers. A 20 mg single dose of omeprazole (Losec) enteric‐coated capsules or tablets was orally administered to 656 healthy subjects from eight subcenters. The polymorphic alleles of CYP2C19 *2, *3, and *17 were determined by Sanger sequencing and Agena mass array. Plasma concentrations of omeprazole were determined by high‐performance liquid‐chromatography tandem mass spectrometry. PK parameters of area under the concentration versus time curve (AUC) 0‐t , AUC from zero to infinity (AUC 0‐∞ ), maximum plasma concentration (C max ), and terminal half‐life (t 1/2 ) were significantly influenced by CYP2C19 phenotype (all p < 0.001) and diplotype (all p < 0.001), and the same results were obtained in the subgroup analysis of the effects of diet and dosage form. The polymorphisms of CYP2C19*2 (rs4244285; all PK parameters p < 0.001) and *3 (rs4986893; p Cmax = 0.020, and the p values of other PK parameters were less than 0.001) were significantly associated with the PKs of omeprazole. For CYP2C19 *17 (rs12248560), only t 1/2 showed a significant correlation ( p = 0.032), whereas other PK parameters did not. The present study demonstrated that the Pks of omeprazole is greatly influenced by CYP2C19 .