EFFICACY OF IVERMECTIN AGAINST STRONGYLOIDES-STERCORALIS INFECTION INJIRDS (MERIONES-UNGUICULATUS)

The activity and distribution of ivermectin (IVM), a broad spectrum an thelmintic for various nematodes and arthropods, was tested against St rongyloides stercoralis infection in the jird (Meriones unguiculatus.) The pattern of IVM concentration in the serum of jirds after either l ow- (200 mu g/kg) or high-dose (1000 mu g/kg) treatment by intraperito neal injection showed a typical single-peak profile with the maximum d rug levels detected at 1 h followed by a rapid decline to undetectable values by 48 h posttreatment. With equivalent IVM doses, the serum le vels in male jirds were significantly higher than those observed in fe male jirds at 1 and 12 h posttreatment (P < 0.05). Low-dose IVM treatm ent of either male or female jirds, in comparison with that of the res pective control groups, produced no observable effect on the adult wor m burden or the parasite fecundity. The curative dose for S. stercoral is in both sexes of animals was achieved when using the high dose of 1 000 mu g/kg of IVM. The area under the curve calculated from the serum -concentration profiles in males was significantly higher than that fo r females after the high-dose treatment of IVM (P < 0.05). By low-dose treatment, a significantly lower adult worm burden was observed in ma les compared with that in females (P < 0.05), and this difference corr elated with the higher serum levels of IVM in male animals. The distri bution of IVM in the jird after high-dose treatment was characterized by initial appearances at 1 h of maximum levels of the drug in the ser um and intestinal content. The maximum level in the feces was reached at 12 h posttreatment and rapidly declined thereafter. The level in th e intestinal tissue was comparatively much lower than that in the inte stinal content and the feces. The half-life of IVM in the intestinal c ontent (49.5 h) was longer than those in the serum, feces, and intesti nal tissue (6.53-13.07 h). Analyses of the relationship between the pe ak serum IVM occurring at 1 h posttreatment and the adult worm recover y revealed that the minimal serum concentration associated with cleara nce of the adult worm from the jird was approximately 0.65 mu g/ml. Th e jird-S. stercoralis model has not only made studies on various aspec ts of parasite biology possible, but also provided an in vivo system t o examine the efficacy as well as the mode of action of IVM against th is intestinal nematode. (C) 1998 Academic Press.