Introduction: Atazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce ATV exposure. We studied ATV pharmacokinetic parameters among children who received ATV/r co-administered with TDF.
Methods: HIV-infected children aged 6-18 years with a body weight of 25-50 kg were eligible. Branded ATV 200 mg/capsule were taken with generic ritonavir 100 mg/tablet once daily plus TDF and lamivudine. A 24-hour pharmacokinetic (PK) study was performed at week 4 at t=0 (pre-dose), 2, 4, 6, 8, 10, 12 and 24 hours. Pharmacokinetic parameters were calculated using non-compartmental methods with WinNonlin software. Targeted ATV AUC0-24 was 15 mg*h/L and Ctrough was 0.15 mg/L. Comparisons of geometric means of ATV pharmacokinetic parameters between different weight bands were made using regression models.
Results: Eighteen HIV-infected children with a median (IQR) age of 13 (11-14) years were enrolled. Median (range) body weight and body surface area were 35 (25-42) kg and 1.21 (0.96-1.35) m2, respectively. Median (IQR) CD4 cell count was 735 (540-1233) cells/mm3. Median (range) of ATV was 164 (145-209) mg/m2. Geometric mean (SD) ATV AUC0-24 was 35.05 (1.06) mg*h/L, and ATV Ctrough was 0.31 (1.13) mg/L. No child had ATV AUC0-24 or Ctrough below target levels. There were no significant differences in PK parameters among weight bands.
Conclusion: ATV/r 200/100 mg dosing provided adequate ATV AUC0-24 when used with TDF in HIV-infected Thai children weighing between 25-50 kg.
(C) 2014 by Lippincott Williams & Wilkins, Inc.