by Palic S, Kip AE, Beijnen JH, Mbui J, Musa A, Solomos A, Wasunna M, Olobo J, Alves F, Dorlo TPC. Journal of Antimicrobial Chemotherapy 2020; doi: 10.1093/jac/dkaa314
Summary: Conventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis is less effective in children than in adults. Results of a trial on a higher allometric dose (median 3.2 mg/kg/day) in paediatric visceral leishmaniasis patients in Eastern Africa showed an unforeseen, lower than dose-proportional increase in exposure. The authors describe a pooled model-based analysis of the paediatric data available from both dosing regimens to characterize the non-linearities in miltefosine pharmacokinetics. The bioavailability of miltefosine appeared to be affected by the cumulative dose, possibly as a consequence of impaired absorption. Despite this, allometric dosing led to a faster target achievement and increased exposure compared with conventional dosing.