Browsing by Author "Ogburn, Evan"

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    Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
    (Springer Nature, 2014) Michaud, Veronique; Kreutz, Yvonne; Skaar, Todd; Ogburn, Evan; Thong, Nancy; Flockhart, David A.; Desta, Zeruesenay; Medicine, School of Medicine
    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 20mg oral dose of omeprazole with a single dose (600mg) or after multiple doses (600mg/day for 17 days) of efavirenz. 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 LC/MS/MS. 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.