Ketoconazole interacts with 14-_ demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone.
Ketoconazole, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent.
Hepatotoxicity, LD50=86 mg/kg (orally in rat)