The pharmacokinetics of nelfinavir in HIV-1-infected children.
The authors investigated the steady-state plasma pharmacokinetics of nelfinavir in HIV-1-infected children in a dosage of 30 mg/kg every 8 hours and 45 mg/kg every 12 hours in 12 HIV-1-infected children (aged 2.1 to 10.8 years) participating in an open-label study of nelfinavir in combination with stavudine and lamivudine. Median values of the primary pharmacokinetic parameters of nelfinavir 30 mg/kg every-8-hours (n = 8) and 45 mg/kg every 12 hours (n = 10) were, respectively, for the area under the plasma concentration-time curve over 24 hours, 90.5 and 71.9 h x microg/mL, for the trough concentration 1.9 and 1.0 microg/mL, and for the maximal concentration 6.3 and 5.2 microg/mL. Overall, a 7-fold interpatient variability was observed for the exposure to nelfinavir. Nelfinavir 30 mg/kg every-8-hours or 45 mg/kg every 12 hours in HIV-1-infected children generally resulted in plasma concentrations higher than those obtained in adults. However, due to a large interpatient variability in the exposure, individual dosage adjustments based on plasma concentrations may be necessary for both dosing regimens to ensure optimal treatment.
van Heeswijk
Rolf P G
RP
Dept. of Pharmacy & Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. rvanheeswijk@ottawahospital.on.ca
Scherpbier
Henriëtte J
HJ
de Koning
Linda A
LA
Heymans
Hugo S A
HS
Lange
Joep M A
JM
Beijnen
Jos H
JH
Hoetelmans
Richard M W
RM
D000284:Administration, Oral; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011208:Powders; D018119:Stavudine / Q000627:therapeutic use; D013607:Tablets
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011208:Powders; D013607:Tablets; D019259:Lamivudine; D018119:Stavudine; D019888:Nelfinavir