title: 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(12)beta of 75.5 +/- 16.9 h, the area under the curve (AUC(0-infinity)) of 1.33 +/- 0.156 microg h ml(-1) and the MRT(0-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(12)beta, 1.67 +/- 0.233 microg h ml(-1) for AUC(0-infinity) and 297 +/- 159 h for MRT(0-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.
authors.affiliation: Kenya Trypanosomiasis Research Institute (KETRI), P.O. Box 362, Kikuyu, Kenya. ketri@net2000ke.com
authors.forename: Grace A
authors.initials: GA
authors.lastname: Murilla
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Peregrine
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ndung'u
authors.forename: Peter H
authors.initials: PH
authors.lastname: Holmes
authors.forename: Mark C
authors.initials: MC
authors.lastname: Eisler
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism* / Q000382:microbiology; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D004996:Ethidium / Q000493:pharmacokinetics*; D008297:Male; D014344:Trypanocidal Agents / Q000493:pharmacokinetics*; D014348:Trypanosoma congolense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000378:metabolism / Q000662:veterinary*
chemical_list: D014344:Trypanocidal Agents; D004996:Ethidium