Shoop W L, DeMontigny P, Fink D W, Williams J B, Egerton J R, Mrozik H, Fisher M H, Skelly B J, Turner M J
Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Int J Parasitol. 1996 Nov;26(11):1227-35. doi: 10.1016/s0020-7519(96)00122-1.
Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel avermectin selected for development as a topical endectocide for all cattle, including lactating cows. The initial efficacy assessments were made in sheep to identify subclasses of the avermectin/milbemycins that possessed inherent activity against a spectrum of nematode parasites. This included examination of several hundred analogs each given orally to a single sheep experimentally infected with a range of parasitic nematodes. Representatives of several subclasses, most notably the 4"-epi-amino avermectin B1 subclass, were identified as possessing potent, broad-spectrum activity against the endoparasites, whereas subclasses such as those with a variety of synthetic substitutions at C-4a or oximes at C-5 were among the least potent. Eprinomectin, 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 other selected avermectin/milbemycins following topical administration to lactating dairy cattle. The molecular structure of each compound had a significant effect on the milk to plasma ratio, but the ratio of each was constant over time, implying an equilibrium between the 2 compartments. Compounds that were saturated at the C-22,23 bond had milk to plasma ratios > or = 1.0, whereas those unsaturated at this bond were generally < or = 1.0. The milk to plasma ratio of eprinomectin was < or = 0.2. Therefore, not only is eprinomectin the most potent broad-spectrum avermectin/milbemycin identified to date, but it also possesses one of the lowest milk partitioning coefficients in this class of antiparasitics.
埃普利诺菌素（MK - 397或4“-表-乙酰氨基-4”-脱氧阿维菌素B1）是一种新型阿维菌素，被选作所有牛（包括泌乳奶牛）的局部用体内外寄生虫驱杀剂进行开发。最初的药效评估在绵羊身上进行，以确定对一系列线虫寄生虫具有内在活性的阿维菌素/米尔倍霉素亚类。这包括对数百种类似物进行检测，每种类似物经口给予一只实验感染多种寄生线虫的绵羊。几个亚类的代表，最显著的是4“-表氨基阿维菌素B1亚类，被确定对体内寄生虫具有强效、广谱活性，而在C - 4a处有各种合成取代基或在C - 5处有肟基的亚类活性最弱。埃普利诺菌素属于4“-表氨基亚类，经口以0.025 mg kg-1的剂量测试时，对一系列线虫具有强效活性。在对泌乳奶牛进行局部给药后，还对这些以及其他选定的阿维菌素/米尔倍霉素进行了乳汁和血浆浓度分析。每种化合物的分子结构对乳汁与血浆的比率有显著影响，但每种化合物的该比率随时间保持恒定，这意味着两个隔室之间存在平衡。在C - 22,23键处饱和的化合物乳汁与血浆的比率≥1.0，而在该键处不饱和的化合物通常≤1.0。埃普利诺菌素的乳汁与血浆比率≤0.2。因此，埃普利诺菌素不仅是迄今为止鉴定出的最有效的广谱阿维菌素/米尔倍霉素，而且在这类抗寄生虫药物中它还具有最低的乳汁分配系数之一。
