Artemether/ Lumefantrine: A Study of the Effect of Local Food on Pharmacokinetics of Lumefantrine and Population Pharmacokinetics of Lumefantrine Among Ugandan Children

This is an observational study with a nested comparative bioavailability study among children based at Mulago Hospital, Kampala Uganda. It is a part of profiled doctoral study project aimed at improving artemether-lumefantrine drug use among children in resource limited settings in order to maximize public health benefits. It involves initial healthy volunteer studies, quantitative analytical studies and finally this pediatric patient study.

Artemether-lumefantrine is currently the first line treatment of uncomplicated malaria in Uganda and several countries in sub Saharan Africa. Currently the recommended dose regimens for children, the most vulnerable population are still empirically weight based derivations based on mainly clinical experience from studies done among adults. Yet children are physiologically different from adults. In particular lumefantrine, a long acting agent ensuring radical cure is highly lipophilic, and has variable oral bioavailability. High variability of lumefantrine uptake and its long half life render it liable to selection pressure if sub-therapeutic concentrations prevail for long periods. Recommended milk or high fat diet to improve its bioavailability may not be available in resource limited settings. In Mwebaza et al ., 2013, our health volunteer crossover bioavailability study preceding the planned patients study, lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. Whereas both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures relative to milk. The greatly improved absorption is attributed to the little fat used to fortify maize porridge. We believe that findings in healthy adult volunteers are relevant for vulnerable African children treated with AL for P. falciparum malaria but this needs to be confirmed.

Objectives

1. To describe the population pharmacokinetics of lumefantrine among under five year old children in Uganda receiving AL for uncomplicated falciparum malaria (Main study).

The described PPK profile will be correlated to treatment outcomes and will form a basis for dose recommendations. 2. To compare the effects of maize porridge plus vegetable oil versus milk on the bioavailability of lumefantrine among under five year old Ugandan children receiving artemether- lumefantrine for uncomplicated falciparum malaria (Nested Study).