Ketoconazole

• IUPAC: (2RS, 4SR ) -1 - ( 4 - {4 - [ -2 - ( 2,4-dichlorophenyl ) -2 - ( imidazol- 1-ylmethyl ) -1,3- dioxolan-4 - ylmethoxy ]-phenyl } piperazin-1 -yl) ethanone
• (±)- cis-1- acetyl-4- {4 - [ cis-2- (2,4- dichlorophenyl ) -2 - (1- imidazolylmethyl ) -1,3- dioxolan-4 - ylmethoxy ] phenyl} piperazine,
• Latin: Ketoconazolum

• J02AB02
• D01AC08
• G01AF11

White to off- white powder

Antifungal

Inhibition of the biosynthesis of ergosterol for fungi

146 ° C

Practically insoluble in water, slightly soluble in dichloromethane, soluble in methanol, sparingly soluble in ethanol

Risk

166 mg · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Ketoconazole is a drug that is used for the prevention and treatment of fungal infections of the skin.

History

Ketoconazole was discovered in 1976 and put on the market early 80s. It was the first orally applicable antifungal agent.

Application

The medication is used particularly in subjects with disease of the immune system such as AIDS, infections due to autoimmune diseases. Examples of treatable with the drug diseases are the seborrheic eczema or pityriasis versicolor the ( Tinea ).

Ketoconazole is used for example in anti-dandruff shampoos. There are several strong doses of the agent. The shampoo can be used like a normal shampoo when it is rinsed thoroughly after application. As part of a pregnancy should be avoided for safety reasons on the application because in animal studies occurred a teratogenic effects at high doses.

Ketoconazole is in pharmacies; Dosage forms for systemic use (tablets) are also available on prescription in most countries.

Likewise, ketoconazole is used in the so-called Cushing's disease. It inhibits the production of cortisol and is used when operative measures are not possible.

Operation

Ketoconazole inhibits the production of ergosterol, which is the main constituent of the cell membrane of the pathogen. The mode of action is inhibition of cytochrome P450 -dependent enzymes, resulting in both the hepatotoxicity, as well as its use in Cushing's disease can be explained. The synthesis of adrenal hormones (eg cortisol) on different occasions of cytochrome P450 -dependent enzymes.

Treatable pathogens

Ketoconazole inhibits the growth of dermatophyte and yeast fungi such as Candida albicans. Resistance to ketoconazole are known in some Candida albicans strains.

Side effects

The EMA wants to ban the oral ketoconazole due to the strong liver damage. The FDA, in contrast, only out warnings for use of oral ketoconazole.

Due to its side effects ketoconazole increasingly replaced by newer fungicides such as fluconazole and / or itraconazole replaced.

Chemical Properties

Ketoconazole is a white to yellowish powder having a melting temperature of 146 ° C. It is highly lipophilic and very slightly soluble in water. It is an imidazole derivative, is generally to the group of azoles.

Stereoisomerism

From the structural formula of ketoconazole will be appreciated that the molecule at the 1,3- dioxolane ring has two stereogenic centers in the 2 - and containing in the 4-position. Theoretically, there are therefore the following four stereoisomers: the (2S, 4R )-form and its mirror image (2R, 4S )-form and the (2S, 4S )-form and its mirror image (2R, 4R)- form. As the drug racemate ( 1:1 mixture ) of the enantiomeric (2S, 4R)- form and (2R, 4S) is used shape, which is also referred to as cis-form or racemic (±)- cis-form.

The (2R, 4R )-form and the (2S, 4S )-form have no practical significance.