Population pharmacokinetic modeling and simulation of amprenavir following fosamprenavir/ritonavir administration for dose optimization in HIV infected pediatric patients.
J Clin Pharmacol
; 54(2): 206-14, 2014 Feb.
Article
de En
| MEDLINE
| ID: mdl-25272370
ABSTRACT
Fosamprenavir (FPV) is the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV). A pediatric population pharmacokinetic model for APV was developed and simulation was used to identify dosing regimens for pediatric patients receiving FPV in combination with ritonavir (RTV) which resulted in concentrations similar to those in adults receiving FPV/RTV 700/100 mg BID. Pharmacokinetic data was obtained from HIV infected subjects aged 2 months to 18 years receiving either FPV or FPV/RTV. A two-compartment model with first order absorption and elimination was an appropriate structural model. Significant covariates in the model included RTV coadministration on clearance, fed status on bioavailability for the oral suspension, body weight on clearance and volume terms, black race on clearance, and age on clearance. The following FPV/RTV twice daily dosing regimens in pediatric patients delivered plasma APV exposure similar to adults 45/7 mg/kg in patients weighing <11 kg, 30/3 mg/kg in patients weighing 11 to <15 kg, 23/3 mg/kg in patients weighing 15 to <20 kg, and 18/3 mg/kg in patients weighting ≥20 kg. Additionally children weighing ≥39 kg can receive the adult regimen.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Organophosphates
/
Sulfonamides
/
Simulation numérique
/
Carbamates
/
Promédicaments
/
Infections à VIH
/
Inhibiteurs de protéase du VIH
/
Ritonavir
/
Modèles biologiques
Limites:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Langue:
En
Journal:
J Clin Pharmacol
Année:
2014
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique