Miconazole

Structural formula
	1: 1 mixture of ( R ) -form (left) and ( S ) -form (right)
General
Non-proprietary name	Miconazole
other names	( RS ) -1- [2,4-dichloro-β- (2,4-dichlorobenzyloxy) phenethyl] imidazole
Molecular formula	C 18 H 14 Cl 4 N 2 O
Brief description	white to almost white, polymorphic powder
External identifiers / databases
ECHA InfoCard	100.041.188
PubChem	4189
DrugBank	DB01110
Wikidata	Q410534
Drug information
ATC code	D01 AC02 ; G01 AF04 ; A01 AB09 ; J02 AB01 ; S02 AA13 ; A07 AC01 ;
Drug class	Antifungal drugs
properties
Molar mass	416.13 g · mol -1
Physical state	firmly
Melting point	83-87 ° C ; 178-184 ° C (mononitrate)
pK s value	6.91
solubility	very sparingly soluble in water, slightly soluble in methanol , soluble in ethanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-317
	P: 280
Toxicological data	550 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Miconazole is a drug from the imidazole group that is used in the treatment of fungal diseases ( mycoses ).

The isomer of miconazole, isoconazole , is also a fungistatic substance .

Clinical information

Application areas (indications)

Miconazole is used to treat fungal infections of the skin (including skin folds) and the mucous membrane. It is effective against practically all skin fungi in humans, as well as against trichomonads and some gram-positive bacteria such as staphylococci and streptococci . Gram-negative bacteria are not affected.

Type and duration of application

It is used for at least 14 days, if necessary until it is no longer possible to grow fungi from skin samples.

Drug interactions

Since the substance is practically not absorbed through the skin, interactions can only occur with other locally applied drugs (dilution, etc.). When used vaginally, the effects of oral anticoagulants can be increased.

Use during pregnancy and breastfeeding

The vaginal use in the first trimester may increase the abortion rate and is therefore relatively contraindicated. Oral use during pregnancy is possible because of the almost non-existent absorption into the body. The breast should not be treated while breastfeeding.

Adverse effects (side effects)

Local irritations of the skin or mucous membranes can mainly occur. Liver damage can occur with systemic uptake. Intolerance or overdose can lead to diarrhea or vomiting. No systemic side effects are known when applied locally. Miconazole and other azole preparations inhibit the enzyme steroid 17α-hydroxylase , which can lead to a temporary decrease in testosterone levels.

Dosage forms

Miconazole is used as a cream or solution, and lozenges, buccal tablets and vaginal suppositories are also available.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Miconazole inhibits enzymes, including lanosterol demethylase , which are required for the synthesis of the ergosterol necessary for the construction of the cell membrane . This increases the permeability of the cell membrane so that vital cell components can escape. In addition, some metabolic functions are hindered in mushrooms. The mean inhibitory concentration is 1–4 µg / ml.

Absorption and distribution in the body (pharmacokinetics)

Miconazole is mainly used locally on the skin or mucous membrane. There is hardly any resorption .

However, there are also oral gels (e.g. Daktar or Micotar) that can be swallowed. In the case of enteral intake, the substance is metabolized in the liver via cytochrome P450 enzymes.

toxicology

The content of commercial creams and solutions is hardly sufficient to cause poisoning in adults. Liver damage can occur if large quantities are consumed.

Stereoisomerism

Miconazole contains a stereocenter, so it is chiral . So there are two enantiomers , ( R ) - and ( S ) -1- {2- (2,4-dichlorophenyl) -2 - [(2,4-dichlorobenzyl) oxy] phenylethyl} imidazole. The drug miconazole is used as a racemate [1: 1 mixture of the ( R ) form and the ( S ) form]. Of these, the ( R ) -form is more effective than the ( S ) -form.

history

Miconazole was patented by Janssen in 1970 and brought onto the market in 1971. It was the first azole preparation effective against deep mycoses .

Trade names

Monopreparations

Castellani solution with Miconazol (D), Daktar (D), Daktarin (A, CH), Fungur M (D), Miconazol KSK (D), Gyno-Daktar (D), Gyno-Mykotral (D), Infectosoor oral gel ( D), Loramyc (D), Micobeta (D), Micotar (D), Monistat (CH), Mykoderm (D), Mycotin (D), Sebolox (CH), Vobamyk (D), various generics (D)

Combination preparations

Acne Plus (D, CH), Daktacort (CH), Decoderm bivalent (CH), Decoderm tri (D), Infectosoor Zinksalbe (D), Micotar ZP (D), Surolan (vet.) (D), Vobaderm (D) ,

literature

Red List 2009
Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 255 f.

Web links

Entry on miconazole at Vetpharm, accessed on August 11, 2012.

Individual evidence

↑ ^a ^b ^c ^d data sheet MICONAZOLE CRS (PDF) at EDQM , accessed on May 8, 2009.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Entry on miconazole. In: Römpp Online . Georg Thieme Verlag, accessed on July 16, 2019.
↑ ^a ^b data sheet (±) -Miconazole nitrate salt from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).

[Ph._Eur.-1] ta sheet MICONAZOLE CRS (PDF) at EDQM , accessed on May 8, 2009.

[römpp-2] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Entry on miconazole. In: Römpp Online . Georg Thieme Verlag, accessed on July 16, 2019.

[Sigma-3] ta sheet (±) -Miconazole nitrate salt from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).