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

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 metab...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2017-12, Vol.61 (12)
Main Authors: Eloy, Philippine, Tessier, Adrien, Fan-Havard, Patty, Chou, Monidarin, Verstuyft, Céline, Taburet, Anne-Marie, Haas, David W, Bertrand, Julie
Format: Article
Language:English
Subjects:
Adult
Anti-HIV Agents
Anti-HIV Agents - therapeutic use
Antiviral Agents
Asians - genetics
Cambodia
Cytochrome P-450 CYP2B6
Cytochrome P-450 CYP2B6 - genetics
Female
HIV Infections
HIV Infections - drug therapy
Humans
Male
Nevirapine
Nevirapine - metabolism
Nevirapine - pharmacokinetics
Nevirapine - therapeutic use
Polymorphism, Single Nucleotide - genetics
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Summary: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 polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00733-17