A comparative study of the biological activities of arprinocid and arprinocid-1-N-oxide

The livers of chickens maintained on a diet containing an effective in vivo level (70 ppm) of arprinocid, an anticoccidial agent, were found to contain 0.64 ppm of this drug and 0.33 ppm of a metabolite, arprinocid-1-N-oxide. When arprinocid was tested against Eimeria tenella in cultures of chick kidney epithelial cells, which do not metabolize the drug appreciably, it was found to block the development of the parasite with an ID50 of 20 ppm. In the same test system, the 1-N-oxide blocks coccidial development with an ID50 of 0.30 ppm. These observations strongly suggest that it is the 1-N-oxide and not arprinocid itself which is the active anticoccidial moeity when arprinocid is fed to the chickens. The action of arprinocid in kidney epithelial cells is partially reversed by excess hypoxanthine, an observation consistent with inhibition of transmembrane transport of purines as the in vitro mechanism of action of this compound. On the other hand, the in vitro anticoccidial action of the 1-N-oxide is not reversed by excess hypoxanthine. Moreover, the 1-N-oxide is less effetive than arprinocid as a purine transport inhibitor. It follows that the anticoccidial action of arprinocid-1-N-oxide is not principally a consequence of inhibition of purine transport.