title: Evaluation of nevirapine dosing recommendations in HIV-infected children.
abstract: OBJECTIVE
  Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used for chronic human immunodeficiency virus infections in adults and children. The aims of this study were to investigate the population pharmacokinetics of NVP in children, establish factors that influence NVP pharmacokinetics and evaluate the current dosing recommendations.
  
  
  METHODS
  Concentrations were measured on a routine basis in 94 children aged from 2 months to 17 years. A total of 390 NVP plasma concentrations were retrospectively collected, and a population pharmacokinetic model was developed with Monolix 4.0.
  
  
  RESULTS
  Nevirapine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. After standardization to a 70 kg adult using allometry, postmenstrual age had a significant effect on the bioavailability. Estimates of apparent clearance and volume of distribution were 3.9 l h(-1) (70 kg)(-1) and 140 l (70 kg)(-1) , respectively. Based on simulations of European Medicines Agency (EMA) and World Health Organization (WHO) dosing recommendations, the probability of observing minimal concentrations below the efficacy target of 3 mg l(-1) is higher following the EMA recommendations than the WHO recommendations. However, NVP underdosing persists for the 3-6 and 6-10 kg weight ranges following the WHO recommendations.
  
  
  CONCLUSIONS
  It is suggested to increase doses to 75 and 100 mg twice daily for the 3-6 and 6-10 kg weight ranges, respectively, in order to obtain more than 95% of children with concentrations above 3 mg l(-1) .
authors.affiliation: EA 3620-Université Paris Descartes Sorbonne Paris Cité, Unité de RechercheClinique, Hôpital Tarnier, 89 rue d’Assas, Paris, France. frantz.foissac@cch.aphp.fr
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.forename: Eric
authors.initials: E
authors.lastname: Lachassinne
authors.forename: Catherine
authors.initials: C
authors.lastname: Dollfus
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D014018:Tissue Distribution
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine