AIM To study the relation of CYP2C19 genotype to omeprazole metabolism in Chinese healthy subjects. METHODS Plasma concentrations
of omeprazole and its main metabolites in 25 subjects were measured for 24 h by high pressure liquid
chromatography after administration of 20 mg omeprazole capsule and pharmacokinetic parameters were calculated by 3p97 software. RESULTS Of the 25 individuals who took part in the pharmacokinetic profile of omeprazole, 7 were homozygous for the wild-type(wt) allele homo EMS (wt/wt; pattern G1), 12 were heterozygous for the CYP2C19 m1, hetero EMS (wt/m1; pattern G2), and 6 were homozygous for the CYP2C19 m1, PMS(m1/m1; pattern G3). The mean clearance values of omeprazole in patterns G1, G2 and G3 were 22.9, 12.7 and 4.9 mL·h -1, respectively. The area under the serum concentration-time curve(AUC) of omeprazole in pattern G1, G2 and G3 were 1.09, 1.47 and 4.87 mg·L -1·h, respectively. There were significant (P<0.05-0.01) differences in the disposition kinetics of omeprazole between the subjects with patterns G1, G2 and the subjects with patterns G3. CONCLUSION There were polymorphism in the 5-
hydroxylation pathway of omeprazole. The 5-hydroxylation pathway of omeprazole is clearly impaired in subjects with m1/m1 than in subjects with wt/wt, wt/m1 and wt/m2.