title: Population pharmacokinetics of tenofovir in HIV-1-infected pediatric patients.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of tenofovir in children and the influence of covariates [body weight (BW), age, cotreatments]. The main goal was then to suggest for the first time the dose of tenofovir disoproxil fumarate (TDF) to give in children.
  
  
  METHODS
  Tenofovir concentrations were monitored on a routine basis and measured in 93 children aged 5 to 18 years; 283 tenofovir plasma concentrations were used to perform a population pharmacokinetic analysis.
  
  
  RESULTS
  A 2-compartment model adequately described the data. A BW allometric scaling was used; and the typical population estimates (interindividual variability), standardized for 70 kg, for apparent clearance, central and peripheral volume of distribution, intercompartmental clearance, and absorption rate constant, were 59.8 L·h⁻¹ (0.48), 386 L (1.39), 666 L, 92.8 L·h⁻¹ and 0.43 h⁻¹, respectively. TDF clearance increased significantly with BW and decreased with lopinavir/ritonavir (LPV/r) coadministration, thus these factors were used to propose doses for children. Dosing scheme, according BW and LPV/r coadministration were simulated to produce the same 24-hr exposure as adults after 300-mg TDF dose.
  
  
  CONCLUSIONS
  Children without LPV/r should receive: 150 mg TDF from 20 to 30 kg, 225 mg TDF from 30 to 40 kg, and the adult dosage of 300 mg TDF over 40 kg. To avoid risk of renal toxicity, TDF dose should be decreased when coadministrated with LPV/r, children should receive 150 mg TDF from 20 to 40 kg, 225 mg TDF from 40 to 55 kg, and the adult dosage of 300 mg TDF over 55 kg.
authors.affiliation: EA 3620, Université Paris Descartes, Sorbonne Paris Cité France, Paris, France. naim.bouazza@cch.aphp.fr
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rey
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine