This study was designed to verify the in vivo efficacy of sulfoxide and sulfone 
fexinidazole metabolites following oral administration in a murine model of 
Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma 
cruzi were treated orally once per day with each metabolite at doses of 10 to 
100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored 
throughout, and cures were detected by parasitological and PCR assays. The 
results were compared with those achieved with benznidazole treatment at the 
same doses. Fexinidazole metabolites were effective in reducing the numbers of 
circulating parasites and protecting mice against death, compared with untreated 
mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both 
metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 
mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was 
detected only in animals treated with the higher dose of 100 mg/kg/day (80%). 
Single-dose pharmacokinetic parameters for each metabolite were obtained from a 
parallel group of uninfected mice and were used to estimate the profiles 
following repeated doses. Pharmacokinetic data suggested that biological 
efficacy most likely resides with the sulfone metabolite (or subsequent reactive 
metabolites formed following reduction of the nitro group) following 
administration of either the sulfoxide or the sulfone and that prolonged plasma 
exposure over the 24-h dosing window is required to achieve high cure rates. 
Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of 
acute infection, with cure rates superior to those achieved with either 
fexinidazole itself or benznidazole.