In vitro metabolism of moxidectin in Haemonchus contortus adult stages

We studied the implication of cytochrome P450 enzymes in the in vitro metab olism of moxidectin (MXD) in homogenates of Haemonchus contortus adult stag es (susceptible isolate, Weybridge, UK). After homogenisation in a phosphat e buffer, 2 ml of homogenates (equivalent to 1 g of nematodes) were incubat ed with 5 mug [C-14] MXD at 37 degreesC for 24 h. MXD and its metabolites w ere separated by HPLC with radiodetection on-line. Only one metabolite was detected and its production was inhibited by carbon monoxide. This result d emonstrates that the cytochrome P450 system is implicated in the metabolisa tion of MXD in H. contortus susceptible to milbemycin. Furthermore, this me tabolite did not match those previously described in vertebrates.