title: Population pharmacokinetics of atazanavir/ritonavir in HIV-1-infected children and adolescents.
abstract: OBJECTIVE
  To investigate atazanavir (ATV) population pharmacokinetics in children and adolescents, establish factors that influence ATV pharmacokinetics and investigate the ATV exposure after recommended doses.
  
  
  METHODS
  Atazanavir concentrations were measured in 51 children/adolescents during a mean therapeutic monitoring follow up of 6.6 months. A total of 151 ATV plasma concentrations were obtained, and a population pharmacokinetic model was developed with NONMEM. Patients received ATV alone or boosted with ritonavir.
  
  
  RESULTS
  Atazanavir pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The effect of bodyweight was added on both apparent elimination clearance (CL/F) and volume of distribution using allometric scaling. Atazanavir CL/F was reduced by ritonavir by 45%. Tenofovir disoproxil fumarate (TDF) co-medication (300 mg) increased significantly by 25% the atazanavir/ritonavir (ATV/r) CL/F. Mean ATV/r CL/F values with or without TDF were 8.9 and 7.1 L h(-1) (70 kg)(-1), respectively. With the recommended 250/100 mg and 300/100 mg ATV/r doses, the exposure was higher than the mean adult steady-state exposure in the bodyweight range of 32-50 kg.
  
  
  CONCLUSIONS
  To target the mean adult exposure, children should receive the following once-daily ATV/r dose: 200/100 mg from 25 to 39 kg, 250/100 mg from 39 to 50 kg and 300/100 mg above 50 kg. When 300 mg TDF is co-administered, children should receive (ATV/r) at 250/100 mg between 35 and 39 kg, then 300/100 mg over 39 kg.
authors.affiliation: EA 3620 Université Paris Descartes, Paris, France. frantz.foissac@gmail.com
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Catherine
authors.initials: C
authors.lastname: Dollfus
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Firtion
authors.forename: Corinne
authors.initials: C
authors.lastname: Laurent
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008954:Models, Biological; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir; D014018:Tissue Distribution
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir