CP-72,588, a semisynthetic analog of the polyether ionophore UK-58,582 with increased anticoccidial potency.

We have employed semisynthesis to enhance the anticoccidial potency of a polyether ionophore. CP-72,588 is the alpha-methyl analog of the fermentation-derived polyether ionophore UK-58,852. The parent ionophore required a dose of 15 ppm to achieve anticoccidial efficacy in chickens equivalent to that of salinomycin at 60 ppm. CP-72,588 demonstrated substantially improved potency, with efficacy at 5 to 7.5 ppm. The intrinsic antimicrobial potencies of the two ionophores are similar; however, CP-72,588 was found in chicken tissues at higher levels than those of the parent ionophore when each was administered at the same dose (8 ppm). The enhanced potency of CP-72,588 may be partially due to enhanced uptake into tissues.

In vivo expression of in vitro anticoccidial activity.

Large-scale screening has led to the identification of several experimental compounds that have very potent intrinsic activity against coccidia, but the lack of translation to in vivo efficacy has been a major hurdle in developing such leads into effective new drugs. We developed methods to explore the impact of oral availability and appropriate distribution in tissue, both of which are potentially important factors in the expression of activity in vivo. For the compounds that we examined, neither oral absorption nor distribution to the site of infection appeared to be the critical barrier to in vivo expression of intrinsic anticoccidial activity. Elucidation of the nature of additional factors that might be involved could assist greatly in the identification of useful new anticoccidial agents.