Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent

V. Michaud, Y. Kreutz, Todd Skaar, E. Ogburn, N. Thong, D. A. Flockhart, Zeruesenay Desta

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Efavirenz increases CYP2C19- and CYP3A-mediated omeprazole metabolism. We hypothesized that CYP2C19 and CYP2B6 genetic polymorphisms influence the extent of induction of omeprazole metabolism by efavirenz. Healthy subjects (n=57) were administered a single 20 mg oral dose of omeprazole on two occasions: with a single 600 mg efavirenz dose; and after a 17-day treatment with efavirenz (600 mg per day). DNA was genotyped for CYP2C19*2, *3 and *17 alleles and CYP2B6*6, *4 and *9 alleles using Taqman assays. Omeprazole, its enantiomers and metabolites were measured by liquid chromatography/tandem mass spectrometry. Our results showed that efavirenz increased omeprazole clearances in all CYP2C19 genotypes in non-stereoselective manner, but the magnitude of induction was genotype dependent. Metabolic ratios of 5-hydroxylation of omeprazole were reduced in extensive and intermediate metabolizers of CYP2C19 (P<0.05). No significant associations were observed between CYP2B6 genotypes and induction by efavirenz on omeprazole metabolism. Our data indicate how interplays between drug interactions and CYP2C19 genetic variations may influence systemic exposure of CYP2C19 substrates.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalPharmacogenomics Journal
Volume14
Issue number2
DOIs
StatePublished - 2014

Fingerprint

efavirenz
Omeprazole
Genotype
Alleles
Cytochrome P-450 CYP3A
Genetic Polymorphisms
Hydroxylation
Tandem Mass Spectrometry
Cytochrome P-450 CYP2C19
Drug Interactions
Liquid Chromatography
Healthy Volunteers

Keywords

  • CYP2B6
  • CYP2C19
  • CYP3A
  • Efavirenz
  • Genetic polymorphisms
  • Omeprazole

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics
  • Medicine(all)

Cite this

Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent. / Michaud, V.; Kreutz, Y.; Skaar, Todd; Ogburn, E.; Thong, N.; Flockhart, D. A.; Desta, Zeruesenay.

In: Pharmacogenomics Journal, Vol. 14, No. 2, 2014, p. 151-159.

Research output: Contribution to journalArticle

Michaud, V. ; Kreutz, Y. ; Skaar, Todd ; Ogburn, E. ; Thong, N. ; Flockhart, D. A. ; Desta, Zeruesenay. / Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent. In: Pharmacogenomics Journal. 2014 ; Vol. 14, No. 2. pp. 151-159.
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