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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Evaluation of ketoconazole.

The pharmacology, microbiology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and drug interactions of ketoconazole are reviewed. Ketoconazole, a new orally active antifungal agent, is an imidazole derivative structurally related to miconazole and clotrimazole. It impairs the synthesis of ergosterol (the main sterol in fungal cell membranes) in susceptible organisms, including yeast (Candida and Cryptococcus spp.), fungi, and dermatophytes. Ketoconazole is absorbed from the gastrointestinal tract; it is better absorbed from acidic aqueous solutions, so drugs that alter the pH of the stomach affect ketoconazole absorption. Therapeutic plasma concentrations are maintained for several hours following ketoconazole administration. Ketoconazole distributes readily into blood, urine, saliva, joint fluid, sebum, and cerumen; recent data indicate it may penetrate into cerebrospinal fluid as well. Elimination is biphasic, with a half-life of two hours during the first 10 hours following a dose, and a half-life of eight hours thereafter. Ketoconazole is metabolized by the hepatic microsomal oxidation system; metabolites are excreted renally. Ketoconazole is effective in treatment of several local and systemic fungal infections. It is approved by FDA for treating candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole has also shown promise in other conditions not yet approved by FDA, including dermatophytosis, pityriasis versicolor, and vaginal candidosis. Controlled, comparative, double-blind trials of ketoconazole versus older agents are generally unavailable. Nausea and vomiting are the most common adverse effects encountered with ketoconazole. Transient elevations in serum liver enzymes have been noted occasionally. Initial daily ketoconazole dosage is 200 mg taken with a meal; 400 mg daily has been used for some conditions. Ketoconazole is a promising new drug, especially when one considers other available antifungal agents. However, large-scale comparative studies are not yet available; a more definitive evaluation of efficacy and safety, especially when the drug is used for long periods of time, must await more widespread use of ketoconazole.[1]


  1. Evaluation of ketoconazole. Sohn, C.A. Clinical pharmacy. (1982) [Pubmed]
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