EFFICACY IN SHEEP AND PHARMACOKINETICS IN CATTLE THAT LED TO THE SELECTION OF EPRINOMECTIN AS A TOPICAL ENDECTOCIDE FOR CATTLE

Eprinomectin (MK-397 or 4 ''-epi-acetylamino-4 ''-deoxy-avermectin B-1 ) is a novel avermectin selected for development as a topical endectoc ide for all cattle, including lactating cows. The initial efficacy ass essments were made in sheep to identify subclasses of the avermectin/m ilbemycins that possessed inherent activity against a spectrum of nema tode parasites. This included examination of several hundred analogs e ach given orally to a single sheep experimentally infected with a rang e of parasitic nematodes. Representatives of several subclasses, most notably the 4 ''-epi-amino avermectin B-1 subclass, were identified as possessing potent, broad-spectrum activity against the endoparasites, whereas subclasses such as those with a variety of synthetic substitu tions at C-4a or oximes at C-5 were among the least potent. Eprinomect in, a member of the 4 ''-epi-amino subclass, possessed potent activity against the range of nematodes when tested at 0.025 mg kg(-1) per os. Milk and plasma concentration profiles were also made for these and o ther selected avermectin/milbemycins following topical administration to lactating dairy-cattle. The molecular structure of each compound ha d a significant effect on the milk to plasma ratio, but the ratio of e ach was constant over time, implying an equilibrium between the 2 comp artments. Compounds that were saturated at the C-22,23 band had milk t o plasma ratios greater than or equal to 1.0, whereas those unsaturate d at this bond were generally less than or equal to 1.0. The milk to p lasma ratio of eprinomectin was less than or equal to 0.2. Therefore, not only is eprinomectin the most potent broad spectrum avermectin/mil bemycin identified to date, but it also possesses one of the lowest mi lk partitioning coefficients in this class of antiparasitics.