Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants

Background. Nelfinavir dosed at similar to 20 to 30 mg/kg three times a day (TID) in older children provides exposure similar to 750 mg TID in adults. However, the pharmacokinetics (PK) of nelfinavir in infants who are <2 years of age is not well-described. The objective of this study was to determine the pharmacokinetics of nelfinavir in infants <2 years of age. Methods. Nelfinavir concentrations were evaluated in 22 HIIV-infected infants between 15 days and 2 years of age receiving nelfinavir as part of Pediatric ACTG Study 356. Nelfinavir therapy was initiated at similar to 25 mg/kg TID (n = 18) or similar to 55 mg/kg twice a day (n = 4) and given in combination with nevirapine, stavudine and lamivudine. PK samples were obtained predose and 1.5 and 4 h postdose at similar to6-month intervals. Eight infants (all less than or equal to3 months of age) also had intensive PK samples collected at Week 1. Results. The median apparent clearance in the infants with intensive pharmacokinetic sampling was 2.7 liters/h/kg (range, 1.8 to greater than or equal to 10) and was similar between twice a day and TID dosing cohorts. Overall nelfinavir concentrations at all collection times were lower in these infants than previously reported in older pediatric patients. Conclusions. Nelfinavir concentrations in infants are highly variable and lower than those seen in adult or older pediatric populations receiving labeled dosing. Therefore it is necessary to further evaluate nelfinavir safety, effectiveness and pharmacokinetics at higher doses than used among other pediatric populations.