title: Population pharmacokinetic modeling and simulation of amprenavir following fosamprenavir/ritonavir administration for dose optimization in HIV infected pediatric patients.
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.
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: April M
authors.initials: AM
authors.lastname: Barbour
authors.forename: Leonid
authors.initials: L
authors.lastname: Gibiansky
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Wire
mesh_terms: D000293:Adolescent; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D010755:Organophosphates / Q000008:administration & dosage / Q000494:pharmacology*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D011355:Prodrugs; D013449:Sulfonamides; C095108:amprenavir; D019438:Ritonavir; C426859:fosamprenavir
keywords: fosamprenavir; pediatric; population pharmacokinetics