CYP2C19 Genotype and pharmacokinetics of rabeprazole and omeprazole in healthy subjects

Objective:To explore whether the in vivo human metabolic disposition of rabepra-zole and omeprazole is dependent of CYP2C19 polymorphism and to predict the influence of CYP2C19 polymorphism on the acid-inhibitory efficacy of rabeprazole and omeprazole. Methods: This was a ran-domized,open,crossover and comparative study. Thirty-six healthy subjects,whose CYP2C19 genotype status was previously determined by allele-specific polymerase chain reaction amplification, participated in the study. There were twenty-four extensive metabolisers (homo and hetero EMs) , and twelve poor metabolisers (PMs) of them. After a single oral dose 20 mg rabeprazole enteric-coated tablet or 20mg omeprazole capsule in a randomized crossover manner, blood samples were collected at various time-points until 12 hour after administration. The plasma concentrations of the two agents and their metabolites were measured by high-performance liquid chromatography (HPLC),and then the phar-macokinetics disposition of them was analyzed. Results:There were not differences between two groups on Cmax,AUC and Tmax;but the mean t1/2 of thioether-rabeprazole in PMs (3.04±0.83h) was signif-icantly longer than that in EMs (1.92±0.44h) (P0.05). And for omeprazole,apart from Tmax of omeprazole and 5-OH-omeprazole,there were most significant differences of other prarmacokinetic pa-rameters between PMs and EMs (all P0.01). Conclusion:Rabeprazole is dominantly transformed to the thioether metabolite in a nonenzymatical manner, and the pharmacokinetics of rabeprazole less dependent of CYP2C19 polymorphism. The metabolites of omeprazole is highly dependent of CYP2C19 genetic polymorphism and therefore presented a significant differences between extensive metabolizers and poor metabolizers. So there may be less influence of CYP2C19 genetic polymorphism on the acid -inhibitory efficacy of rabeprazole. but there would be of omeprazole.