The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets and syrups in African HIV-infected children
Background: Guidelines recommend lopinavir/ritonavir (LPV/r) as first- and second-line therapy for young and older HIV-infected children, respectively. Available formulations have limitations making their widespread use complex
Methods: An open-label, comparative-bioavailability (randomized cross-over) study compared a novel twice-daily minitab sprinkle formulation (40mg/10mg, Cipla Pharmaceuticals) versus innovator syrup in HIV-infected Ugandan infants 3-
Results: 77 infants/children were included in cohort-A(n=19)/B(n=26)/C(n=32). Among 132 evaluable pharmacokinetic profiles, there were 13/21/25 within-child comparisons in cohort-A/B/C. For minitabs versus syrup, geometric mean (GM)(95%CI) AUC0-12h was 88.6(66.7-117.6) versus 77.6(49.5-121.5) h.mg/L in cohort-A (ratio(GMR)(90%CI)=1.14 (0.71-1.85)) and 138.7 (118.2-162.6) versus 109.1 (93.7-127.1) h.mg/L in cohort-B (GMR(90%CI)=1.27 (1.10-1.46)). For minitabs versus tablets, GM(95%CI) AUC0-12h was 83.1(66.7-103.5) versus 115.6(103.0-129.7) h.mg/L; GMR(90%CI)=0.72(0.60-0.86). Subtherapeutic levels (
Conclusions: LPV/r exposure from minitabs was comparable with syrup, but lower than tablets, with no significant differences in subtherapeutic concentrations. Minitabs were more acceptable than syrups for younger children, but older children preferred tablets.
Musiime, V.; Fillekes, Q.; Kekitiinwa, A.; Kendall, L.; Keishanyu, R.; Namuddu, R.; Young, N.; Opilo, W.; Lallemant, M.; Walker, A.S.; Burger, D.; Gibb, D.M. The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets and syrups in African HIV-infected children. JAIDS Journal of Acquired Immune Deficiency Syndromes (2014) : [DOI: 10.1097/QAI.0000000000000135]