title: Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach.
abstract: OBJECTIVE
  Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor approved and is widely used in combination therapy to treat HIV-1 infection. The pharmacokinetics of nevirapine was extensively studied in various populations with a parametric approach. Hence, this study was aimed to determine population pharmacokinetic parameters in Malaysian HIV-infected patients with a non-parametric approach which allows detection of outliers or non-normal distribution contrary to the parametric approach.
  
  
  METHODS
  Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters' estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC.
  
  
  RESULTS
  The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC.
  
  
  CONCLUSIONS
  In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16100, Kubang Kerian, Kelantan, Malaysia. szn_m@yahoo.com.|Hospital Raja Perempuan Zainab II, Kelantan, Malaysia. szn_m@yahoo.com.
authors.forename: Suzana
authors.identifier: http://orcid.org/0000-0002-5025-2308
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16100, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Wan Nazirah Wan
authors.initials: WN
authors.lastname: Yusuf
authors.affiliation: INSERM UMR 850, Université de Limoges CHU, Limoges, France.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Woillard
authors.affiliation: Institutes for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Tan Soo
authors.initials: TS
authors.lastname: Choon
authors.affiliation: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16100, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Norul Badriah
authors.initials: NB
authors.lastname: Hassan
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D065702:Cytochrome P-450 CYP2B6
keywords: HIV; Nevirapine; Non-parametric; Pharmacokinetics