Exploring CYP2B6 activity by measuring the presence ofnevirapine hydroxy metabolites in plasma

Suzana MUSTAFA, Norul Badriah HASSAN, Soo Choon TAN, Mahiran MUSTAFA, Ahmad Kashfi AB RAHMAN, Lee Lee LOW, Wan Nazirah WAN YUSUF
2016 Turkish Journal of Medical Sciences  
Background/aim: Nevirapine is a reverse-transcriptase inhibitor widely used in combination therapy to treat HIV infection. Nevirapine is extensively metabolized in the liver and CYP2B6 is mainly responsible for oxidation of 3-hydroxynevirapine (3-OH NVP). This study aims to explore CYP2B6 activity by measuring 2-hydroxynevirapine (2-OH NVP) and 3-OH NVP in plasma and to identify factors associated with nevirapine pharmacokinetic parameters. Materials and methods: A total of 112 patients were
more » ... ruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction. Results: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters. Conclusion: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.
doi:10.3906/sag-1503-116 pmid:28081342 fatcat:7tlu7hx4bfbm5pc6767w3twohm