title: Exploring CYP2B6 activity by measuring the presence ofnevirapine hydroxy metabolites in plasma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A total of 112 patients were recruited 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.|Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Norul Badriah
authors.initials: NB
authors.lastname: Hassan
authors.affiliation: Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Soo Choon
authors.initials: SC
authors.lastname: Tan
authors.affiliation: Hospital Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia.
authors.forename: Ahmad Kashfi
authors.initials: AK
authors.lastname: Ab Rahman
authors.affiliation: Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia.
authors.forename: Lee Lee
authors.initials: LL
authors.lastname: Low
authors.affiliation: Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Wan Nazirah
authors.initials: WN
authors.lastname: Wan Yusuf
mesh_terms: D019380:Anti-HIV Agents; D065702:Cytochrome P-450 CYP2B6 / Q000097:blood*; D015658:HIV Infections; D006801:Humans; D019829:Nevirapine; D018894:Reverse Transcriptase Inhibitors
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6
keywords: 2-hydroxynevirapine; 3-hydroxynevirapine; Nevirapine