Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype.

摘要: Objectives To assess the possible relationship between metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4′-hydroxylation phenotype genotype. Methods The pharmacokinetic was investigated in 14 Japanese male volunteers (seven extensive seven poor metabolizers S-mephenytoin). All subjects received a single 40 mg oral dose as enteric-coated formulation. Results An interphenotypic difference observed: mean values for area under concentration-time curve (AUC), elimination half-life (t½), apparent clearance were significantly (p < 0.01) greater, longer, lower, respectively, than metabolizers. The AUC sulfone greater metabolizers, whereas main demethylated metabolite (M2) lower A significant negative correlation observed individual log10% urinary excretion 4′-hydroxymephenytoin (rS = −0.816; p 0.005). CYP2C19 genotyping test results found to be complete accordance with phenotypes. Conclusion These data indicated that is pharmacogenetic control 4′-hydroxylase (CYP2C19). Clinical Pharmacology & Therapeutics (1997) 62, 619–628; doi: