The pharmacokinetics of nelfinavir in HIV-1-infected children

Area of Science:

• Pharmacokinetics
• Pediatric HIV Therapy
• Antiretroviral Drug Exposure

Background:

• Nelfinavir is an antiretroviral protease inhibitor used in HIV-1 treatment.
• Understanding nelfinavir pharmacokinetics in children is crucial for optimizing therapy.
• Previous studies have established nelfinavir pharmacokinetics in adults, but pediatric data is less extensive.

Purpose of the Study:

• To investigate the steady-state plasma pharmacokinetics of nelfinavir in HIV-1-infected children.
• To compare two different nelfinavir dosing regimens: 30 mg/kg every 8 hours and 45 mg/kg every 12 hours.
• To assess interpatient variability in nelfinavir exposure in pediatric patients.

Main Methods:

• An open-label study involving 12 HIV-1-infected children (aged 2.1 to 10.8 years).
• Administration of nelfinavir in combination with stavudine and lamivudine.
• Measurement of key pharmacokinetic parameters including area under the curve (AUC), trough concentration (Cmin), and maximal concentration (Cmax).

Main Results:

• Median AUC values were 90.5 h x microg/mL for the 30 mg/kg every-8-hours regimen and 71.9 h x microg/mL for the 45 mg/kg every-12-hours regimen.
• Median trough concentrations were 1.9 microg/mL and 1.0 microg/mL, respectively.
• A significant 7-fold interpatient variability in nelfinavir exposure was observed, with pediatric concentrations generally higher than in adults.

Conclusions:

• Both nelfinavir dosing regimens (30 mg/kg q8h and 45 mg/kg q12h) achieved plasma concentrations in children that were generally higher than those in adults.
• The substantial interpatient variability in nelfinavir exposure highlights the need for individualized dosage adjustments.
• Therapeutic drug monitoring may be necessary to ensure optimal nelfinavir treatment efficacy and safety in pediatric HIV-1 patients.