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Clinical Trial
. 2017 Nov 22;61(12):e00733-17.
doi: 10.1128/AAC.00733-17. Print 2017 Dec.

Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians

Philippine Eloy  1 , Adrien Tessier  2 , Patty Fan-Havard  3   4 , Monidarin Chou  5 , Céline Verstuyft  6   7   8   9 , Anne-Marie Taburet  7   9 , David W Haas  10   11 , Julie Bertrand  12 ; ANRS12154 Study Group
Collaborators, Affiliations
Clinical Trial

Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians

Philippine Eloy et al. Antimicrob Agents Chemother. .

Abstract

Nevirapine is metabolized by several hepatic cytochrome P450 (CYP) isoforms to generate four primary hydroxylated metabolites: 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, and 12-hydroxynevirapine. The present study characterized associations between genetic polymorphisms and metabolite ratios in HIV-infected Cambodians. We demonstrate associations between CYP2B6 polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.

Keywords: genetic polymorphisms; metabolism pathways; nevirapine; population pharmacokinetics.

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Figures

FIG 1
FIG 1
Box plots of metabolite ratios for 2-hydroxynevirapine (2OH-NVP), 3-hydroxynevirapine (3OH-NVP), 8-hydroxynevirapine (8OH-NVP), and 12-hydroxynevirapine (12OH-NVP) in 127 HIV-infected Cambodians. Bond lines indicate medians, boxes represent interquartile ranges, dashed lines represent 95% confidence interval, and circles represent outliers. Note that the y axis is in log-scale.
FIG 2
FIG 2
Box plots of metabolite ratios for 3OH-NVP (a) and 8OH-NVP (b) stratified by CYP2B6 516G→T (rs3745274) genotype. MR, metabolite ratio; n, number of participants.
See this image and copyright information in PMC

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