The effect of level of feed intake on the pharmacokinetic disposition of oxfendazole in sheep.

Oxfendazole (OFZ) containing a trace of [14C]-OFZ was administered intraruminally and intravenously to sheep fitted with rumen and abomasal cannulae and which were being fed 800 and 400 g of 50:50 lucerne:wheaten chaff daily. The [14C] was extensively associated with rumen particulate digesta, the shorter residence time of digesta in sheep on high compared to low feed intake reduced the duration of OFZ absorption. Abomasal fluid flow was greater in sheep on high than low intake and was attributed to increased gastric secretions. At high intake a greater proportion of the [14C] dose flowed from the abomasum in digesta fluid, but its residence time in the abomasum was of shorter duration compared with low intake. The more rapid passage of digesta through the gastrointestinal tract in the former sheep reduced the duration for drug desorption from particulate material and absorption into the bloodstream. In these high intake sheep and availability of [14C]-compounds in plasma was lower and more rapidly cleared than in sheep on low feed intake. Concomitant with the reduced absorption a greater proportion of the dose was excreted in faeces, and a lower proportion in the urine of sheep on high compared with low feed intake. The extensive association of OFZ and its metabolites with rumen digesta, is a principal determinant of OFZ kinetics.