Imidazoles Ketoconazole

Ketoconazole is less selective for fungal P450 than are the fluconazole and itraconazole (inhibit mammalian cytochrome P450 enzymes).

Clinical use: it has limited use because of the drug interactions, endocrine side effects, and of its narrow therapeutic range. Oral formulation that is best absorbed at a low gastric pH. Ketoconazole is used in treatment of mucocutaneous candidiasis and nonmeningeal coccidioidomycosis. It is also used in the treatment of seborrheic dermatitis and pityriasis versicolor (Topical/ shampoo).

Adverse effects: First, ketoconazole inhibition of human cytochrome P450 enzymes interferes with biosynthesis of adrenal and gonadal steroid hormones, producing significant endocrine effects such as gynecomastia, infertility, and menstrual irregularities. Second, the interaction with P450 enzymes can alter the metabolism of other drugs, leading to enhance toxicity of those agents (eg. increased levels and enhanced arrhythmogenic effects of the nonsedating antihistamines, and terfenadine).