Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir treatment in HIV-1-infected children.
BACKGROUND
Once-daily lopinavir/ritonavir (LPV/r) is not approved for treatment of HIV paediatric patients. Once daily treatment in children might serve the same goals of patient comfort and adherence as in adults.


METHODS
HIV type-1-infected children aged 6 months to 18 years, who were virologically suppressed on an LPV/r-containing regimen, were eligible. Treatment 1 consisted of once-daily LPV/r 460/115 mg/m(2), plus two nucleoside reverse transcriptase inhibitors (NRTIs). Treatment 2 consisted of twice-daily LPV/r 230/57.5 mg/m(2) plus two NRTIs. Patients were randomized either to start with treatment 1 followed by treatment 2 or vice versa. Full pharmacokinetic profiles were analysed for lopinavir and ritonavir with a validated HPLC tandem mass spectrometry assay.


RESULTS
Seven patients (five girls and two boys) were included in the study. Median age was 9.8 years (range 5.8-15.5). For the once-daily treatment, the median (range) lopinavir 24 h area under the plasma -concentration-time curve (AUC(24 h)), maximum plasma concentration (C(max)) and 24 h plasma concentration (C(24 h)) were 214.6 h*mg/l (114.2-289.2), 13.5 mg/l (8.3-17.5) and 3.4 mg/l (0.6-7.4), respectively. For the twice-daily treatment the median (range) lopinavir 12 h area under the plasma concentration-time curve (AUC(12 h)), C(max) and 12 h plasma concentration (C(12 h)) were 80.9 h*mg/l (23.3-135.9), 9.8 mg/l (3.4-15.2) and 5.7 mg/l (1.7-9.7), respectively.


CONCLUSIONS
This study suggests that the pharmacokinetics of lopinavir after twice-daily and once-daily dosing are similar, with no observable difference in tolerability, in this group of patients between 5 and 15 years old.
la Porte
Charles
C
Ottawa Health Research Institute, Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada. claporte@ohri.ca
van Heeswijk
Rolf
R
Mitchell
Charles D
CD
Zhang
Guijun
G
Parker
Jackie
J
Rongkavilit
Chokechai
C
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir