Abacavir pharmacokinetics in human immunodeficiency virus-infected children ranging in age from 1 month to 16 years: a population analysis.
Abacavir pharmacokinetics was studied in 105 children by a population approach performed with NONMEM. A 1-compartment open model with linear absorption and elimination adequately described the data. Typical population estimates (percent interindividual variability) of absorption rate constant, apparent distribution volume, and apparent plasma clearance were 1.79 h(-1) (58%), 42.9 L (53%), and 24.3 L/h (30%), respectively. Apparent plasma clearance was positively related to body weight. Individual Bayesian estimates of apparent plasma clearance were used to calculate individual abacavir area under the concentration curve (AUC). For the current weight-based regimen, abacavir exposure was found to be constant throughout the age range of the study, with an overall mean AUC value of 8.5 +/- 2.5 mg x h/L, which is slightly greater than the mean AUC value reported in adults. This study confirms the relevance of the current weight-based abacavir dosage regimen in pediatric patients.
Jullien
Vincent
V
Pharmacologie Clinique, Université René Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, 82 Avenue Denfert-Rochereau, 75674 Paris Cedex 14, France.
Urien
Saïk
S
Chappuy
Hélène
H
Dimet
Jérôme
J
Rey
Elisabeth
E
Pons
Gérard
G
Blanche
Stéphane
S
Tréluyer
Jean-Marc
JM
D000293:Adolescent; D017677:Age Distribution; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir