Oil-Fortified Maize Porridge Increases Absorption of Lumefantrine in Children with Uncomplicated Falciparum Malaria.

Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria. Absorption of lumefantrine (LUM) is fat dependent, and in children, intake is recommended with milk. We investigated whether oil-fortified maize porridge can be an alternative when milk is not available. In an open-label pharmacokinetic study, Ugandan children <5 years with uncomplicated Plasmodium falciparum malaria were randomized to receive standard six-dose AL treatment [one tablet (20 mgA/120 mg LUM) if <15 kg and two tablets if >15 kg] with milk (A) or maize porridge plus oil (B). Parametric two-sample t-test was used to compare relative oral LUM bioavailability. The primary end-point was LUM exposure till 8 hr after the first dose (AUC(0-8 hr)). Secondary outcome included day 7 concentrations (d7(LUM)), LUM exposure between days 7 and 28 (AUC(d7-28)) and day 28 PCR-adjusted parasitological response. Evaluable children (n = 33) included 16 in arm A and 17 in arm B. The AUC(0-8 hr) was comparable between A and B [geometric mean (95% CI): 6.01 (3.26-11.1) versus 6.26 (4.5-8.43) hr*g/mL, p = 0.9]. Less interindividual variability in AUC(0-8 hr) was observed in B (p = 0.01), but d7(LUM) and AUC(d7-28) were comparable. Children receiving two tablets had significantly higher exposure than those receiving one tablet [median d7(LUM) (505 versus 289 ng/mL, p = 0.02) and AUC(d7-28) (108 versus 41 hr*g/mL, p = 0.006)]. One parasitological failure (d28 recrudescence) was observed. Our findings suggest that oil-fortified maize porridge can be an alternative to milk in augmenting absorption of LUM. The lower LUM exposure observed in children dosed with one AL tablet needs further attention.