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 (Bas indicus) cattle were infected with one of two populations of Trypanosoma congolense: one drug-sensitive (ILl180), and one drug-resistant (IL3330). The animals were then treated intramuscularly With homidium bromide at a dose rate of 1.0 mg kg - I 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- I 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 of 75.5 ± 16.9 h. the area under the curve (AUCo_",) of 1.33 ± 0.156 Ilg h ml- I and the MRTo -f. 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 1.67 ± 0.233 Ilg h ml-- I for AUCo _ Cf and 297 ± 159 h for MRTo _ J: 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. (g 2002 Elsevier Science B.Y. All rights reserved.