Diminazene aceturate was administered intravenously at 3.5 mg/kg body weight to mongrel dogs before and after infection with Trypanosoma congolense. Plasma and urine were collected at varying intervals thereafter and analysed for the compound. The mean area under the concentration-time curve (AUC) of diminazene in healthy dogs was 25.8 h.micrograms/ml but was significantly increased (p less than 0.05) to 35.7 h.micrograms/ml after infection with T. congolense. The distribution half-life was significantly reduced (p less than 0.05) in dogs after infection, being 0.12 h compared to 0.17 h in the same dogs before infection. The mean proportion of the diminazene recovered in the urine of infected dogs (25.1%) was not significantly different from that recovered in the urine of healthy dogs (26.8%). These results indicate that infection with T. congolense increases the rate at which diminazene is distributed in the body but that the infection has no marked influence on the urinary excretion of the drug.
The therapeutic activity of diminazene aceturate, difluoromethylornithine (DFMO) and a combination of the two agents was investigated in experimental Trypanosoma brucei brucei infections in mongrel dogs. The criteria used in the assessment of the trypanocidal effect of these compounds included the examination of the blood for the parasite, as well as clinical and haematological changes at intervals following treatment. Diminazene aceturate (7 mg/kg intramuscularly), DFMO (300 mg/kg/day orally in three divided doses for six days) and the combination of diminazene aceturate (7 mg/kg intramuscularly) and DFMO (300 mg/kg/day orally for six days) produced an intermittent aparasitemia in the dogs. Relapse infection occurred in all the three groups, but the period of aparasitemia produced by the combination of the agents was longest. The packed cell volume, haemoglobin concentration and red cell count values decreased after the dogs were inoculated with the parasite. The values improved slightly following the treatments with the agents or their combination. The total white blood cell counts in the infected dogs indicated leucocytosis, but this improved with drug treatment.
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