In vitro metabolism of C-14-moxidectin by hepatic microsomes from various species

Moxidectin is an antiparasitic drug widely used in cattle, sheep and compan ion animals. No data were available on its metabolism in wild species or in monogastrics. The in vitro metabolism of C-14-moxidectin was studied using hepatic microsomes from several different species: cow (Bos taurus), sheep (Ovis ovis), goat (Capra hircus), deer (Cervus dama), rat (Rattus norvegic us), pig (Sus scrofa and rabbit (Oryctolagus cuniculus). After separation a nd quantification by HPLC, the extent of metabolism of C-14-moxidectin was greatest with microsomes from sheep (32.7%) as compared to those from cows (20.6%), deer (15.4%), goats (12.7%), rabbits (7.0%) or rats (3.0%). The le ast metabolism occurred with microsomes from pigs, with 0.8% of total detec ted metabolites. A C-29 monohydroxymethyl metabolite was detected in the gr eatest amounts, providing 0.4% out of the total detected radioactivity in p igs and 19.3% in sheep. In addition, the importance of P450 3A in the metab olism of C-14-moxidectin was confirmed by using in vivo induced P450 in com bination with various P450 inhibitors.