|Ketoconazole, a 1: 1 mixture of the stereoisomers (2 S , 4 R ) -ketoconazole (top) and (2 R , 4 S ) -ketoconazole (bottom)|
|Molecular formula||C 26 H 28 Cl 2 N 4 O 4|
white to almost white powder
|External identifiers / databases|
|Mechanism of action|
|Molar mass||531.43 g · mol -1|
146 ° C
|As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .|
The drug is especially used in people with an immune system disease such as AIDS or infections due to autoimmune diseases. Examples of diseases that can be treated with the drug are seborrheic eczema or pityriasis versicolor (bran fungus).
Ketoconazole, for example, in anti- dandruff - shampoos used. There are different strength doses of the remedy. The shampoo can be used like a normal shampoo if it is rinsed out thoroughly after use. To be on the safe side, it should not be used during pregnancy, as animal experiments showed damage to the fruit at high doses.
Ketoconazole is also used for Cushing's disease . It inhibits the production of cortisol and is used when surgical measures are not possible.
Mode of action
Ketoconazole prevents the production of ergosterol , which is the main component of the pathogen's cell membrane . The mode of action is based on the inhibition of cytochrome P450- dependent enzymes, which explains both the hepatotoxicity and the use in Cushing's disease . The synthesis of adrenal hormones (e.g. cortisol ) requires enzymes that are dependent on cytochrome P450 in several places.
Oral ketoconazole is a potent inhibitor of cortisol synthesis due to its ability to inhibit cytochrome P450 enzymes in the adrenal gland . Ketoconazole also has direct effects on corticotropic tumor cells in patients with Cushing's syndrome. Oral ketoconazole is contraindicated in patients with acute or chronic liver disease or if liver enzyme levels are more than twice the upper limit of normal at the start of treatment. Treatment with it must not be continued if symptoms of hepatitis are present or liver enzyme levels are three times the upper limit of normal.
The mechanism of damage to the liver as a result of taking ketoconazole is not fully understood. Due to the risk of hepatotoxicity, marketing authorization for oral ketoconazole as an antifungal agent was suspended in October 2013.
Ketoconazole is a white to yellowish powder with a melting temperature of 146 ° C. It is highly lipophilic and very sparingly soluble in water. It is an imidazole derivative and generally belongs to the group of azole fungicides .
From the structural formula of ketoconazole it can be seen that the molecule on the 1,3-dioxolane ring contains two stereocenters in the 2- and 4-position. Theoretically there are four stereoisomers : The (2 S , 4 R ) form and the mirror image (2 R , 4 S ) form as well as the (2 S , 4 S ) form and the mirror image (2 R , 4 R ) shape. As a drug , a is a racemate (1: 1 mixture) of the mutually enantiomeric (2 S , 4 R ) -form and the (2 R , 4 S ) -form used, also known as racemic cis -form or (±) - cis Shape is called.
The (2 R , 4 R ) form and the (2 S , 4 S ) form have no practical significance.
- Nizoral (CH, D), Terzolin (D), Ket (D), Ketozolin (D), Fungoral (A), Lur (CH), Ninazol (Th)
- European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
- Entry on ketoconazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .
- Entry on ketoconazole in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
- Entry on ketoconazole. In: Römpp Online . Georg Thieme Verlag, accessed on January 8, 2015.
- ABDA database.
- DS Loose, PB Kan, MA Hirst, RA Marcus and D. Feldman: Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest. 1983; 71 (5): pp. 1495-1499. PMC 437014 (free full text) doi: 10.1172 / JCI110903 .
- European Medicines Agency recommends suspension of marketing authorizations for oral ketoconazole
- Information letter on ketoconazole 200 mg tablets (Nizoral® tablets) (PDF; 72 kB) Drug Commission of the German Medical Association of August 22, 2013.
- FDA Drug Safety Communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems
- HRA Pharma Germany: Rote-Hand-Brief on Ketoconazole HRA® (Ketoconazole): Risk of hepatotoxicity. (PDF) Medicines Commission of the German Medical Association, accessed on May 25, 2015 .