ketoconazole

ketoconazole, antifungal drug used to treat skin and bodily infections caused by various types of fungi. Ketoconazole mainly targets yeasts, such as Candida, which infect the skin, and dermatophytes, such as species of Trichophyton and Microsporum, which infect keratinized tissues, such as skin, hair, and nails. However, the drug also works against certain dimorphic fungi and molds, including Histoplasma capsulatum and Blastomyces dermatitidis, which can cause serious systemic infections.

Ketoconazole is classified as an imidazole antifungal, owing to its five-membered heterocyclic ring structure containing two nitrogen atoms. Imidazole compounds disrupt the synthesis of ergosterol, which is an essential component of the fungal cell membrane, helping to maintain membrane fluidity and structural integrity. Thus, a lack of ergosterol weakens the membrane and renders it dysfunctional, which ultimately results in fungal cell death.

Ketoconazole is applied topically or is administered orally. Topical preparations are available in the form of creams, gels, lotions, or shampoos. Such preparations are applied directly to the skin to treat athlete’s foot, ringworm, seborrheic dermatitis, and other fungal infections of the skin. Oral ketoconazole is prescribed for severe systemic fungal infections, such as blastomycosis (caused by B. dermatitidis) and histoplasmosis (caused by H. capsulatum). It generally is used as a last resort in these cases, such as when other antifungal drugs are ineffective or unavailable, because of the risk of severe side effects, namely its ability to cause potentially fatal liver damage.

Because of the high risk of liver toxicity, oral ketoconazole has been withdrawn from the market in some places, including in Australia, China, and Europe. Other countries, such as Canada and the United States, have placed restrictions on its use. Topical ketoconazole, on the other hand, is considered safe and remains widely available for over-the-counter or prescription use.