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

Abstract
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.
AuthorsF W Jennings
JournalTropical medicine and parasitology : official organ of Deutsche Tropenmedizinische Gesellschaft and of Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ) (Trop Med Parasitol) Vol. 42 Issue 3 Pg. 157-60 (Sep 1991) ISSN: 0177-2392 [Print] Germany
PMID1801135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Arsenicals
  • Nitroimidazoles
  • Trypanocidal Agents
  • MK 436
  • Suramin
  • melaminylthioarsenate
Topics
  • Animals
  • Arsenicals (therapeutic use)
  • Brain Diseases (drug therapy)
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Mice
  • Nitroimidazoles (therapeutic use)
  • Suramin (therapeutic use)
  • Trypanocidal Agents (therapeutic use)
  • Trypanosoma brucei brucei
  • Trypanosomiasis, African (drug therapy)

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