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

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...

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Main Authors:	Michaud, Veronique, Kreutz, Yvonne, Skaar, Todd, Ogburn, Evan, Thong, Nancy, Flockhart, David A., Desta, Zeruesenay
Format:	Online
Language:	English
Published:	2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740059/

id	pubmed-3740059
recordtype	oai_dc
spelling	pubmed-37400592014-10-01 Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent Michaud, Veronique Kreutz, Yvonne Skaar, Todd Ogburn, Evan Thong, Nancy Flockhart, David A. Desta, Zeruesenay Article 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 CYP2C192, 3 and 17 alleles and CYP2B66, 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. 2013-04-30 2014-04 /pmc/articles/PMC3740059/ /pubmed/23629159 http://dx.doi.org/10.1038/tpj.2013.17 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Michaud, Veronique Kreutz, Yvonne Skaar, Todd Ogburn, Evan Thong, Nancy Flockhart, David A. Desta, Zeruesenay
spellingShingle	Michaud, Veronique Kreutz, Yvonne Skaar, Todd Ogburn, Evan Thong, Nancy Flockhart, David A. Desta, Zeruesenay Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
author_facet	Michaud, Veronique Kreutz, Yvonne Skaar, Todd Ogburn, Evan Thong, Nancy Flockhart, David A. Desta, Zeruesenay
author_sort	Michaud, Veronique
title	Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
title_short	Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
title_full	Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
title_fullStr	Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
title_full_unstemmed	Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype-dependent
title_sort	efavirenz-mediated induction of omeprazole metabolism is cyp2c19 genotype-dependent
description	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 CYP2C192, 3 and 17 alleles and CYP2B66, 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.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740059/
_version_	1612002187796283392

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

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