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

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)beta of 75.5 +/- 16.9 h, the area under the curve (AUC(0-infinity)) of 1.33 +/- 0.156 mug h ml(-1) and the MRT0-infinity 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)beta, 1.67 +/- 0.233 mug h ml(-1) for AUC(0-infinity) and 297 +/- 159 h for MRT0-infinity 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. (C) 2002 Elsevier Science B.V. All rights reserved.