Evaluation of the relationship between polymorphisms in CYP2C19 and the single-dose pharmacokinetics of omeprazole in healthy Chinese volunteers: A multicenter study.

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) , AUC from zero to infinity (AUC ), maximum plasma concentration (C ), and terminal half-life (t ) 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 CYP2C192(rs4244285; all PK parameters p < 0.001) and 3(rs4986893; p  = 0.020, and the p values of other PK parameters were less than 0.001) were significantly associated with the PKs of omeprazole. For CYP2C1917 (rs12248560), only t 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.