Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged ≥7 years

Background: The Asian population, in general, has higher antiretroviral concentrations than those who are not Asian, but there are limited pharmacokinetic data for darunavir/ritonavir in Asian children. Methods: Thai children aged >= 7 years and with body weight (BW)>= 20 kg who were on darunavir/ritonavir for >= 2 weeks underwent 12-h pharmacokinetics with blood sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing. Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to <30 kg, n=12), 450/100 mg twice daily (BW 30 to <40 kg, n=2) or 600/100 mg twice daily (BW >= 40 kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution. Results: Of the 19 children, 8 were female, median age was 13 years (range 7-16) and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment was 11 months. The geometric mean values for darunavir were 60.3 hxmg/l for the area under the concentration-time curve at 0-12 h (AUC(0-12)), 8.3 mg/l for the maximum concentration (C-max) and 3.1 for the concentration prior to the next dose (C-12) with no differences between dosing groups. All had C-12 above the protein binding adjusted 50% effective concentration (EC50) of protease inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters were similar to those in non-Asian individuals from the DELPHI study, in which 13 of 20 with BW<40 kg used 50 or 60 mg ritonavir boosting. Conclusions: Thai children aged >= 7 years who were on standard darunavir dosing with 100 mg ritonavir boosting had adequate and comparable darunavir AUC(0-12), Cmax and C-12 to non-Asian children who mainly used lower doses of ritonavir boosting. A ritonavir boosting dose of 100 mg can be used for children weighing >= 20 kg, particularly when lower dose formulations are unavailable or if intolerant to the solution.