Terconazole. Pharmacology of a new antimycotic agent

Terconazole belongs to a new chemical class of antifungal agents, the triazoles. It was designed and synthesized to be more active than the imidazoles. The basic mechanism of action of terconazole, inhibition of fungal cytochrome P-450, is similar to that of the imidazoles. However, because of the additional nitrogen atom in the triazole ring and the lipophilic tail, terconazole establishes a firmer and longer-lasting link with the membrane-bound fungal cytochrome P-450. In addition, terconazole is more metabolically stable and less vulnerable to oxidation and conjugation than are the imidazoles. Terconazole has far greater selectively for yeast cytochrome P-450 than for mammalian microsomal cytochrome P-450. The spectrum of terconazole's in vitro activity includes a wide range of pathogenic fungi; in Eagle's Minimum Essential Medium, fungicidal activity against all strains of Candida albicans occurred at less than or equal to 100 ng/mL. In a rat model of severe vaginal candidiasis, terconazole was more potent than all the imidazoles tested. The high affinity and selectivity of terconazole for fungal cytochrome P-450 and its potent in vitro and in vivo activity indicate that the drug may well become a significant agent for the treatment of fungal disease.