Role of animal and human pharmacology in antifungal drug design.

Abstract

Since the late sixties, several new antifungal drugs have become available. Initially, they were all intended for topical use, and, consequently, animal and human pharmacology always primarily aimed at confirming therapeutic efficacy. With the new tendency for the development of orally active antifungal drugs, human and animal pharmacology have significantly gained in importance. Indeed, not only is it now necessary to demonstrate the presence of adequate antifungal concentrations at the site of infection, but the systemic availability of the antifungal drug also necessitates an in-depth study of the effects of the drug on the function of several organs. As a result, human and animal pharmacology have become the cornerstones in the selection of orally active antifungal drugs. The development of ketoconazole has been an example of the need for optimized pharmacological screening. The choice of itraconazole--with its improved tissue affinity, its lower therapeutic dose requirements, and its increased selectivity for fungal cytochrome P-450--demonstrates very well that the use of animal and human pharmacology helps in the design of an antifungal drug with as much effect as possible on the fungus and as little effect as possible on the host.