title: Age-related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysis.
abstract: OBJECTIVE
  To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations.
  
  
  METHODS
  The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses.
  
  
  RESULTS
  Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h(-1) (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg(-1) for children less than 2 weeks, 1.23 mg kg(-1) for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg(-1), 1 mg kg(-1), and 30 mg, respectively).
  
  
  CONCLUSIONS
  Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults.
authors.affiliation: Université Paris Descartes-Faculté de Médecine, France. vincent.jullien@svp.aphp.fr
authors.forename: V
authors.initials: V
authors.lastname: Jullien
authors.forename: A
authors.initials: A
authors.lastname: Raïs
authors.forename: S
authors.initials: S
authors.lastname: Urien
authors.forename: J
authors.initials: J
authors.lastname: Dimet
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
authors.forename: M
authors.initials: M
authors.lastname: Bouillon-Pichault
authors.forename: E
authors.initials: E
authors.lastname: Rey
authors.forename: G
authors.initials: G
authors.lastname: Pons
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: J M
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D008954:Models, Biological; D018119:Stavudine / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018119:Stavudine