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

Clin Pharmacol Ther. 1995 Jun;57(6):662-9. doi: 10.1016/0009-9236(95)90229-5.


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 S/R 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 S/R 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Genotype
  • Humans
  • Hydroxylation
  • Male
  • Mephenytoin / pharmacokinetics*
  • Middle Aged
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism*
  • Omeprazole / pharmacokinetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Reference Values


  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Mephenytoin