The effects of drug-sensitive and drug-resistant Trypanosoma congolense infections on the pharmacokinetics of homidium in Boran cattle

Abstract

Two groups of five Boran ( Bos indicus) cattle were infected with one of two populations of Trypanosoma congolense; one drug-sensitive (IL1180), and one drug-resistant (IL3330). The animals were then treated intramuscularly with homidium bromide at a dose rate of 1.0 mg kg −1 bodyweight 7 days after trypanosomes were detected in the peripheral blood of all the five animals in each group. Following treatment of cattle infected with drug-sensitive trypanosomes, parasites could no longer be detected in the bloodstream of four out of five cattle after 24 h, and after 48 h for the fifth animal. The animals remained aparasitaemic up to the end of the observation period of 90 days and serum drug concentrations determined by enzyme-linked immunosorbent assay (ELISA) remained above the detection limit of 0.1 ng ml −1 for the entire period. Following treatment of cattle infected with drug-resistant trypanosomes, parasites did not disappear from the bloodstream in any of the five animals. The rate of drug elimination was greater in cattle infected with drug-resistant trypanosomes and the drug was no longer detectable approximately 3 weeks after treatment. Non-compartmental pharmacokinetic analysis showed that the values for t 1 2 β of 75.5±16.9 h, the area under the curve (AUC 0−∞) of 1.33±0.156 μg h ml −1 and the MRT 0−∞ of 32.8±4.45 h obtained in cattle infected with the drug-resistant trypanosome population were significantly lower than the values of 424±146 h for t 1 2 β, 1.67±0.233 μg h ml −1 for AUC 0−∞ and 297±159 h for MRT 0−∞ obtained in cattle infected with the drug-sensitive population. The persistence of drug-resistant infections in cattle following homidium treatment was associated with more rapid drug elimination than in those in which infections with drug-sensitive parasites were cleared by the drug.