Chemotherapy of CNS-trypanosomiasis: combination chemotherapy with a 5-nitroimidazole (MK 436), an arsenical (Cymelarsan) and suramin.

A detailed study of the combined effect of suramin, MK 436 (5-nitroimidazole) and Cymelarsan (melaminylthioarsenate) was investigated in the murine CNS-trypanosomiasis model. Using a combination of Cymelarsan and MK 436 without preliminary suramin, complete cures were obtained with a 2 day treatment of 15.0 mg/kg MK 436 and 5.0 mg/kg Cymelarsan. If the MK 436 was reduced to 10 mg/kg then 4 consecutive daily treatments were required. If the Cymelarsan was reduced to 2.5 mg/kg either a 3 day treatment in combination with 15.0 mg/kg or a 4 day treatment with 10 mg/kg MK 436 was necessary. Utilizing the single suramin (20 mg/kg) dose followed by combined MK 436/Cymelarsan a 2 day treatment with 10 mg/kg (or twice daily 5.0 mg/kg) MK 436 and 2.5 mg/kg Cymelarsan gave complete cures. Maximum cure rate for suramin followed by a one day treatment with 15 mg/kg MK 436 and 5.0 mg/kg Cymelarsan was 4/6 mice, indicating that a one day treatment regimen might be possible with slightly increases dose rates of the two trypanocides. A two day treatment period for CNS-trypanosomiasis is therefore feasible with the dose levels used in these experiments provided a combination chemotherapeutic regimen of suramin, MK 436, Cymelarsan are employed.