Fexinidazole is a 5-nitroimidazole drug currently in clinical development for 
the treatment of human sleeping sickness (human African trypanosomiasis [HAT]), 
caused by infection with species of the protozoan parasite Trypanosoma brucei. 
The compound and its two principal metabolites, sulfoxide and sulfone, have been 
assessed for their ability to kill a range of T. brucei parasite strains in 
vitro and to cure both acute and chronic HAT disease models in the mouse. The 
parent molecule and both metabolites have shown trypanocidal activity in vitro 
in the 0.7-to-3.3 μM (0.2-to-0.9 μg/ml) range against all parasite strains 
tested. In vivo, fexinidazole is orally effective in curing both acute and 
chronic diseases in the mouse at doses of 100 mg/kg of body weight/day for 4 
days and 200 mg/kg/day for 5 days, respectively. Pharmacokinetic data indicate 
that it is likely that the sulfoxide and sulfone metabolites provide most, if 
not all, of the in vivo killing activity. Fexinidazole and its metabolites 
require up to 48 h exposure in order to induce maximal trypanocidal efficacy in 
vitro. The parent drug and its metabolites show no in vitro cross-reactivity in 
terms of trypanocidal activity with either themselves or other known 
trypanocidal drugs in use in humans. The in vitro and in vivo antitrypanosomal 
activities of fexinidazole and its two principal metabolites provide evidence 
that the compound has the potential to be an effective oral treatment for both 
the T. b. gambiense and T. b. rhodesiense forms of human sleeping sickness and 
both stages of the disease.