Metabolite studies of isometamidium in cattle

Isometamidium, a phenathridinium compound, has been used extensively both for prophylaxis and therapy against trypanosomiasis in cattle. The lack of detection of this drug in serum and urine within 24 hours following either i.v. or i.m. administration of the non-labelled drug as opposed to the labelled drug, would suggest either insensitivity of the methods used or rapid metabolism of the drug to compounds which are active against trypanosomes at these concentrations. A preliminary study was carried out using liver, kidney, bile, blood and urine samples from two groups of steers, one of which had been treated with 14C-isometamidium labelled on the homidium molecule and the other with 14C-isometamidium labelled on the benzamidine molecule and slaughtered 21 and 60 days after treatment. Isometamidium was detected in the liver up to 21 days post treatment but was not detected at 47 and 60 days post treatment. Metabolites which corresponded to homidium and benzamidine derivatives were detected in liver, kidney, bile and urine samples. No isometamidium was detected in urine collected 24 hrs after treatment. From this study, it seems that the prohylactic activity of isometamidium is due to homidium and/or its derivatives. (author). 8 refs, 3 tabs