METABOLIC DISPOSITION OF LANSOPRAZOLE IN RELATION TO THE S-MEPHENYTOIN 4'-HYDROXYLATION PHENOTYPE STATUS

Objective: To assess the possible involvement of CYP2C19 in the metabo lism of lansoprazole in vivo. Methods: Sixteen male Korean subjects, w ho had been phenotyped as extensive metabolizers and poor metabolizers of S-mephenytoin 4'-hydroxylation polymorphism (n = 8 each) with race mic mephenytoin with use of the 8-hour urine analysis of 4'-hydroxymep henytoin, took an oral dose of 30 mg lansoprazole, and blood samples w ere collected up to 48 hours after dosing. Lansoprazole and its metabo lites were measured by high-performance liquid chromatography with ult raviolet detection. Results: The mean lansoprazole area under the conc entration-time curve (AUC), elimination half-life (t(1/2)), and appare nt oral clearance (CLoral) were significantly (p < 0.001) greater, lon ger, and lower, respectively, in the poor metabolizer than in the exte nsive metabolizer group. The mean values for the AUC of hydroxylansopr azole and AUC ratio of hydroxylansoprazole to lansoprazole were signif icantly (p < 0.01 to p < 0.001) less in the poor metabolizer than in t he extensive metabolizer group, whereas those for the AUC of lansopraz ole sulfone and ratio of lansoprazole sulfone to lansoprazole were gre ater (p < 0.001) in the former than in the latter group. In addition, the log(10) 4'-hydroxymephenytoin excreted in urine correlated signifi cantly (P < 0.01) with the CLoral of lansoprazole. Conclusions: These results suggest that the hydroxylation of lansoprazole cosegegates wit h the genetically determined S-mephenytoin 4'-hydroxylation (CYP2C19) polymorphism in the Korean subjects.