Doramectin — a potent novel endectocide

Abstract

Doramectin, 25-cyclohexyl-5- O-demethyl-25-de(1-methylpropyl) avermectin A 1a, was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. The primary evaluation of its in vivo antiparasitic activity was carried out using a rat Trichostrongylus colubriformis model and a rabbit Psoroptes cuniculi model. In each case the new avermectin performed favourably relative to dihydroavermectin B 1a (DHAVM), the major component of ivermectin. Doramectin was extensively evaluated in cattle using an experimental micelle formulation, proving highly effective in cattle infected with Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus when administered subcutaneously at 200 μg kg −1. The plasma pharmacokinetic characteristics of doramectin in cattle following intravenous administration revealed a plasma half-life of approximately 89 h. In the micelle formulation, doramectin administered subcutaneously at 400 μg kg −1 provided persistent activity against infection of cattle with C. oncophora and O. ostertagi for at least 8 and 12 days respectively.