Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent.

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Michaud V, Kreutz Y, Skaar T, Ogburn E, Thong N, Flockhart DA, Desta Z

Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent.

Pharmacogenomics J. 2014 Apr;14(2):151-9. doi: 10.1038/tpj.2013.17. Epub 2013 Apr 30.

PubMed ID

23629159 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Efavirenz	Cytochrome P450 2C19	Protein	Humans	Unknown	Inducer	Details