title: The disposition of antiparasitic drugs in relation to the development of resistance by parasites of livestock.
abstract: The kinetic and dynamic disposition of endo- and ectoparasiticides in livestock in relation to development of resistance is examined. Based on the modes of action of antiparasitic drugs, maximum activity necessitates that the parasite be exposed to 'toxic' concentrations for as great a duration as possible. In contrast, exposure to non-lethal discriminating drug concentrations has a significant potential to promote the development of resistance. Orally administered anthelmintics quickly associate with particulate digesta in the rumen; their subsequent desorption from particulate matter as it vacates the rumen maintains the duration of metabolite availability. The flow rate of digesta increases with feed intake and the presence of gastrointestinal parasites, and together with other parasite-induced physiological changes to the gut, contributes to reduced duration of drug availability. The potential for orally administered drugs to bypass the rumen, due to closure of the oesophageal groove, exacerbates the effect. Once absorbed, the metabolite concentration with time profile progressively decreases, the rate depending upon the chemical nature of the drug and the type and condition of the host into which it was administered. The greater hepatic activity of goats speeds drug elimination, the lower dose equivalent availability increases the potential for generation of drug resistance in parasites of goats as compared to sheep. Parasites whose resistance is generated in goats may be then transferred to sheep. Similar distribution/elimination kinetics apply to topically administered insecticides of sheep. The progressively reducing concentrations expose ectoparasites to discriminating drug levels, again contributing to the development of resistance. It is anticipated that a greater understanding of the physiological/pharmacological effects which are described in this review will permit the more efficient use of existing and future antiparasitic drugs.
authors.affiliation: CSIRO Division of Animal Health, McMaster Laboratory, Glebe, NSW, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Hennessy
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000829:Animals, Domestic / Q000378:metabolism / Q000469:parasitology*; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D004351:Drug Resistance; D010271:Parasites / Q000187:drug effects*; D010272:Parasitic Diseases / Q000188:drug therapy / Q000378:metabolism; D010273:Parasitic Diseases, Animal; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D000981:Antiprotozoal Agents