title: No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors.
abstract: OBJECTIVE
  A prospective population pharmacokinetic study of nevirapine (NVP) was performed to test the relationship between hepatotoxicity and NVP trough plasma concentration and to identify which covariates could influence NVP pharmacokinetics.
  
  
  METHODS
  All patients [77 HIV-1 (human immunodeficiency virus type 1)-infected patients (128 samples)] were either on first-line antiretroviral therapy or switched from successful therapy containing protease inhibitor. Population pharmacokinetic parameters were estimated by a non-linear mixed-effect modelling method. Hepatotoxicity was evaluated by ASAT (aspartate aminotransferase) plasma level.
  
  
  RESULTS
  No correlation was found between high NVP trough plasma concentration and high ASAT level or the increase of ASAT level on NVP therapy. Age and Caucasian race were found to be significant covariates of NVP clearance (Cl/F). Population pharmacokinetic parameters (rate absorption constant=1.04 h(-1); Cl/F=3.31 h(-1); apparent volume of distribution=92 l) are consistent with previous studies.
  
  
  CONCLUSIONS
  High NVP trough plasma concentrations are not correlated with hepatotoxicity in our population. NVP clearance is decreased in the elderly patients, suggesting a potential increase of NVP plasma level and the interest of therapeutic drug monitoring for this population.
authors.affiliation: Department of Pharmacology, Hôtel Dieu, 9 Quai Moncousu, 44093 Nantes cedex, France. eric.dailly@chu-nantes.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Eric
authors.initials: E
authors.lastname: Billaud
authors.forename: Véronique
authors.initials: V
authors.lastname: Reliquet
authors.forename: Sébastien
authors.initials: S
authors.lastname: Breurec
authors.forename: Philippe
authors.initials: P
authors.lastname: Perré
authors.forename: Sophie
authors.initials: S
authors.lastname: Léautez
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
authors.forename: François
authors.initials: F
authors.lastname: Raffi
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D001499:Bayes Theorem; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D001219:Aspartate Aminotransferases