The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: A population study

We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism, Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers, Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the SIR ratio of mephenytoin in an 8-hour urine collection, Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing, All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance, Omeprazole hydroxylation correlated with the SIR ratio of mephenytoin in extensive metabolizers (r² = 0.681; p < 0.001), Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism.