title: Population pharmacokinetics of nevirapine in Thai HIV-infected patients.
abstract: BACKGROUND
  Nevirapine-based antiretroviral therapy is widely used as a first-line treatment for HIV-infected patients in resource-limited settings. Nevirapine plasma concentration has been shown to be associated with virological response and treatment failure. Therefore, identifying sources of the variability of nevirapine pharmacokinetics is important for dose optimization. The purpose of the current study was to determine the population mean pharmacokinetic parameters and identify factors that influence pharmacokinetic parameters of nevirapine in Thai HIV-infected patients.
  
  
  METHODS
  The model was developed by a non-linear mixed-effects modelling approach using NONMEM. Model validation was performed using bootstrap analysis and external validation. Additionally, nevirapine plasma concentrations of 200 mg twice daily (NVPBID) and 400 mg once daily (NVPOD) were simulated using the final model to investigate the impact of the covariates and different dosage regimens on nevirapine steady state concentrations.
  
  
  RESULTS
  The apparent clearance (CL/F) of nevirapine estimated from this population was 2.51 l/h which is lower than the values previously reported in other populations. The concomitant use of rifampicin increased CL/F by 20%. Simulated nevirapine plasma concentrations from NVPBID were superior to the NVPOD regimen.
  
  
  CONCLUSIONS
  This population-based pharmacokinetic model can be used for optimizing nevirapine dosage regimens for individual patients to improve efficacy and safety of nevirapine therapy in this population.
authors: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors: Thanaporn
authors: T
authors: Wattanakul
authors: Anchalee
authors: A
authors: Avihingsanon
authors: Weerawat
authors: W
authors: Manosuthi
authors: Baralee
authors: B
authors: Punyawudho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066264:Datasets as Topic; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013785:Thailand; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine