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

John D. Balian, Nadia Sukhova, James W. Harris, Jan Hewett, Linda Pickle, Joyce A. Goldstein, Raymond L. Woosley, David A. Flockhart

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)662-669
Number of pages8
JournalClinical pharmacology and therapeutics
Volume57
Issue number6
DOIs
StatePublished - Jun 1995

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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