title: Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients.
abstract: OBJECTIVE
  To study the possible influence of patient characteristics on abacavir pharmacokinetics.
  
  
  METHODS
  A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM.
  
  
  RESULTS
  Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1), respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg.
  
  
  CONCLUSIONS
  The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies.
authors.affiliation: Pharmacologie Clinique, Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assitance Publique-Hôpitaux de Paris, Paris, France. Vincent.jullien@svp.ap-hop-paris.fr
authors.forename: V
authors.initials: V
authors.lastname: Jullien
authors.forename: J-M
authors.initials: JM
authors.lastname: Tréluyer
authors.forename: H
authors.initials: H
authors.lastname: Chappuy
authors.forename: J
authors.initials: J
authors.lastname: Dimet
authors.forename: E
authors.initials: E
authors.lastname: Rey
authors.forename: N
authors.initials: N
authors.lastname: Dupin
authors.forename: D
authors.initials: D
authors.lastname: Salmon
authors.forename: G
authors.initials: G
authors.lastname: Pons
authors.forename: S
authors.initials: S
authors.lastname: Urien
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics*; D013607:Tablets; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D000099227:Abacavir