Hennessy D R, Ali D N, Tremain S A
CSIRO Division of Animal Health, McMaster Laboratory, Glebe, N.S.W. Australia.
Int J Parasitol. 1994 May;24(3):327-33. doi: 10.1016/0020-7519(94)90079-5.
The disposition of oxfendazole (OFZ) containing a trace of [14C]OFZ was examined in the gastrointestinal tract and bloodstream of sheep fitted with rumen and abomasal cannulae. Within 2 h of intraruminal (IR) administration, OFZ and its metabolites were almost completely associated with rumen particulate digesta. The proportion of metabolites in digesta fluid increased with their passage from the rumen into the abomasum. To determine the fate of 14C-labelled metabolites after distribution throughout rumen digesta, the rumen particulate and fluid digesta phases from a donor sheep were separated and each transferred to the rumen of an untreated recipient sheep. The 14C-labelled metabolites which derived from the donor rumen fluid quickly associated with recipient rumen particulate material. The metabolites were then progressively desorbed, as were metabolites which were transferred already associated with rumen particulate digesta. Desorption occurred faster in the abomasum than in the rumen. There was no difference in uptake kinetics between administration routes, indicating rapid equilibrium. Consequently the disposition of [14C] OFZ and its metabolites in the bloodstream was similar in each group. It is suggested that the progressive desorption of particulate associated metabolites is a principal determinant of the duration of OFZ availability.
在装有瘤胃和皱胃套管的绵羊的胃肠道和血液中,研究了含有微量[14C]奥芬达唑(OFZ)的奥芬达唑的处置情况。瘤胃内(IR)给药后2小时内,OFZ及其代谢产物几乎完全与瘤胃颗粒性消化物结合。随着它们从瘤胃进入皱胃,消化液中代谢产物的比例增加。为了确定14C标记的代谢产物在整个瘤胃消化物中分布后的去向,将供体绵羊的瘤胃颗粒和液体消化物相分离,并分别转移到未处理的受体绵羊的瘤胃中。来自供体瘤胃液的14C标记的代谢产物迅速与受体瘤胃颗粒物质结合。然后,这些代谢产物逐渐解吸,已经与瘤胃颗粒性消化物结合转移的代谢产物也是如此。解吸在皱胃中比在瘤胃中发生得更快。给药途径之间的摄取动力学没有差异,表明达到了快速平衡。因此,每组中[14C]OFZ及其代谢产物在血液中的处置情况相似。有人认为,颗粒结合代谢产物的逐渐解吸是奥芬达唑可利用时间长短的主要决定因素。