THE DISPOSITION OF ANTIPARASITIC DRUGS IN RELATION TO THE DEVELOPMENTOF RESISTANCE BY PARASITES OF LIVESTOCK

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 neccss itates that the parasite be exposed to 'toxic' concentrations for as g reat a duration as possible. In contrast, exposure to non-lethal discr iminating drug concentrations has a significant potential to promote t he development of resistance. Orally administered anthelmintics quickl y associate with particulate digesta in the rumen; their subsequent de sorption from particulate matter as it vacates the rumen maintains the duration of metabolite availability. The flow rate of digesta increas es with feed intake and the presence of gastrointestinal parasites, an d together with other parasite-induced physiological changes to the gu t, 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 met abolite concentration with time profile progressively decreases, the r ate depending upon the chemical nature of the drug and the type and co ndition of the host into which it was administered. The greater hepati c activity of goats speeds drug elimination, the lower dose equivalent availability increases the potential for generation of drug resistanc e in parasites of goats as compared to sheep. Parasites whose resistan ce is generated in goats may be then transferred to sheep. Similar dis tribution/elimination kinetics apply to topically administered insecti cides of sheep. The progressively reducing concentrations expose ectop arasites to discriminating drug levels, again contributing to the deve lopment of resistance. It is anticipated that a greater understanding of the physiological/pharmacological effects which are described in th is review will permit the more efficient use of existing and future an tiparasitic drugs.