Abstract:
Paediatric drug formulations of artemisinin combination therapies and pharmacokinetic data supporting their use in African children are urgently needed for the effective treatment of young children suffering from falciparum malaria in sub-Saharan Africa. In this thesis the pharmacokinetic characteristics of two paediatric formulations of artesunate-mefloquine therapy were evaluated in the treatment of uncomplicated malaria in paediatric patients. Twenty-four patients were assigned to treatment with either a fixed-dose paediatric granule co-formulation (10 – 20 kg bodyweight) or a co-blister tablet formulation of artesunate-mefloquine (>20 – 40 kg bodyweight). Median values for Cmax (861and 930 ng/ml), Tmax (1.5 and 1.5 h) and AUC0-t (2050 and 2470 h*ng/ml) were comparable for dihydroartemisinin in the two groups. Exploratory analysis of mefloquine plasma levels revealed a trend towards higher concentrations in the younger age group during the absorption phase (2550 and 1815 ng/ml 54 hours after initiation of treatment, respectively). Median mefloquine concentrations at day 28 were 197 and 343 ng/ml, respectively. The pharmacokinetic characteristics of the two paediatric dosage forms, i.e., the novel fixed-dose co-formulation and the standard co-blister of artesunate-mefloquine show comparable results in the two treatment groups. The novel fixed-dose paediatric formulation is an interesting option for outpatient treatment of uncomplicated malaria in African children.