Pre-clinical Studies of Antifungal Agents for Deep-seated Mycoses

Abstract

The developmental aim of antifungal agents for the treatment of deep seated mycoses is different from that of agents for superficial mycoses in two aspects. The formor must be active against fungal species which are common in deep seated infections not only, in vitro but also when administered systemically with their high bioavailability and safety. This means that their antifungal activities must be evaluable both in vitro and in vivo from an early stage of development. Proper in vitro evaluation of these agents is not easy however, because the results vary from experiment to experiment. A standard method of susceptivility testing were recently recommended for yeast, although not for molds. This method must be confirmed to make a good screening selection. Animal models are another way to determine the real activity of antifungals even at the screening stage, for in vitro tests often fail to provide this information. Pharmacokinetics, metabolism and safety tests are another important means of evaluation of antifungals. There are problems in estimating the results in human beings. The tests also take a lot of work and a long time to complete with some advantages to the existing agents.
Thus, it is easy to understand the difficulties involved in developing new fine antifungal agents. Clear standards including clinical trials are required for their development.