Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth

Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations of all drugs in test combinations were simultaneously varied has been used to identify and quantify drug interactions. The methods have been applied to combinations of two, three, and four drugs, including antineoplastic drugs, antifungal drugs, and combinations of antineoplastic and antifungal drugs. Results were obtained which allow predictions of effects of combinations and provide maximum effectiveness in growth inhibition with minimum levels of the test drugs.