Pharmacokinetics
When administered orally, ketoconazole is best absorbed at highly acidic levels, so antacids or other causes of decreased stomach acid levels will lower the drugs absorption. Absorption can be increased by taking it with an acidic beverage, such as cola. Ketoconazole is very lipophilic and tends to accumulate in fatty tissues. Chemistry
Ketoconazole is a synthetic imidazole. It is a nonsteroidal compound. It is a racemic mixture of two enantiomers, levoketoconazole ((2S,4R)-(−)-ketoconazole) and dextroketoconazole ((2R,4S)-(+)-ketoconazole). Levoketoconazole is under development for potential clinical use as a steroidogenesis inhibitor with better tolerability and less toxicity than ketoconazole. Other steroidogenesis inhibitors besides ketoconazole and levoketoconazole include the nonsteroidal compound aminoglutethimide and the steroidal compound abiraterone acetate. History
Ketoconazole was discovered in 1976 at Janssen Pharmaceuticals. It was patented in 1977, followed by introduction in the United States in July 1981. Following its introduction, ketoconazole was the only systemic antifungal available for almost a decade. Ketoconazole was introduced as the prototypical medication of the imidazole group of antifungals. Oral ketoconazole has been replaced with oral itraconazole for many mycoses.Due to incidence of serious liver toxicity, the use of oral ketoconazole was suspended in France in July 2011 following review. This event triggered an evaluation of oral ketoconazole throughout the rest of the European Union as well. In 2013, oral ketoconazole was withdrawn in Europe and Australia, and strict restrictions were placed on the use of oral ketoconazole in the United States and Canada.
Oral ketoconazole is now only indicated for use in these countries when the indication is a severe or life-threatening systemic infection and alternatives are unavailable. However, topical ketoconazole, which does not distribute systemically, is safe and widely used still.Ketoconazole HRA was approved for use in the European Union for treatment of Cushings syndrome in November 2013.As of March 2019, oral levoketoconazole (developmental code name COR-003, tentative brand name Recorlev) is phase III clinical trials for the treatment of Cushings syndrome. Oral levoketoconazole may have a lower risk of liver toxicity than oral ketoconazole. Society and culture
Generic names
Ketoconazole is the generic name of the drug and its INN, USAN, BAN, and JAN. Brand names
Ketoconazole has been marketed under a large number of brand names. Availability
Ketoconazole is available widely throughout the world.In 2013, the European Medicines Agencys Committee on Medicinal Products for Human Use (CHMP) recommended that a ban be imposed on the use of oral ketoconazole for systemic use in humans throughout the European Union, after concluding that the risk of serious liver injury from systemic ketoconazole outweighs its benefits. Veterinary use
Ketoconazole is sometimes prescribed as an antifungal by veterinarians for use in pets, often as unflavored tablets that may need to be cut to smaller size for correct dosage. References
External links
"Ketoconazole". Drug Information Portal. U.S. National Library of Medicine.