Toxicity and combined therapeutic activity of artemether and lumefantrine in Trypanosoma-brucei-infected rats

Abstract

The combination of artemether and lumefantrine, commonly used for the treatment of human malaria was evaluated for toxicity and anti-trypanosomal efficacy in rats infected with Trypanosoma brucei. Following oral administration, the only sign of toxicity observed was weakness which was very transient. The severity of the symptoms which was dose-related was noted at higher combinations of (artemther 40 mg and lumefantrine 240 mg) and (artemether 80 mg and lumefantrine 480mg). At necropsy, there was no evidence of cumulative effects of the drug combinations on organs and tissues. The therapeutic combinations (artemether 2.5 mg and Lumefantrine 15 mg), (artemether 5 mg and lumefantrine 30 mg) and (artemether 10 mg and lumefantrine 60 mg) showed a graded dose response. These produced anti-trypanosomal effect through reduction in the level of parasitaemia, modulation of decline in packed cell volume (PCV) and the severity of the attendant disease as well as enhanced the survival of the rats. This study is important because for three and half decades there has been no significant progress in the development of new and less toxic trypanocides for the control of both human and animal trypanosomosis. The results therefore, show that the drug combination is less toxic and has a therapeutic effect on  Trypanosoma brucei.