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Effects of trypanosomal infection on the pharmacokinetics of diminazene aceturate in dogs.

Pharmacokinetics of diminazene aceturate (3.5 mg/kg) was investigated in normal mongrel dogs and in those infected with Trypanosoma brucei brucei. After intravenous injection the decrease in concentration followed a biphasic process with mean elimination half-life (t1/2 beta) of 9.87 hr in healthy dogs and 12.51 hr in T. b. brucei infected dogs. The mean total body clearance (cl) of diminazene aceturate in healthy dogs (0.62 l/kg/hr) was significantly lower (p less than 0.05) when compared to that of the infected animals (0.47 l/kg/hr). The distribution half-life (t1/2 alpha) was significantly (p less than 0.05) decreased in dogs after infection (0.14 hr) compared to 0.2 hr observed in the same animals before infection. The mean diminazene recovered in the urine of normal dogs (28.18%) was not significantly different from that recovered from infected dogs (26.1%). These results indicate that infection with T. b. brucei markedly retards the total body clearance of diminazene and also hastens the distribution of the drug when administered intravenously.