Econazole
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-Econazole_Structural_Formulae_of_both_enantiomers.png)
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| 1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom) | |||||||||||||
| General | |||||||||||||
| Non-proprietary name | Econazole | ||||||||||||
| other names | |||||||||||||
| Molecular formula | C 18 H 15 Cl 3 N 2 O | ||||||||||||
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| Drug information | |||||||||||||
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| Mechanism of action |
Inhibition of the biosynthesis of ergosterol in mushrooms |
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| properties | |||||||||||||
| Molar mass | 381.68 g · mol -1 | ||||||||||||
| Physical state |
firmly |
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| density |
1.33 g cm −3 |
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| Melting point |
86.8 ° C |
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| safety instructions | |||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||
Econazol ( trade name : including Pevaryl , first manufacturer was Janssen-Cilag ) is a drug from the group of imidazole derivatives that is used as a topical antifungal agent in the treatment of dermatomycoses (skin fungus).
Clinical information
Application areas (indications)
The fungistatic active ingredient econazole is available in dermatology for topical application in various dosage forms such as cream, lotion, solution, skin milk, spray solution and powder. There is a combination preparation which, in addition to econazole nitrate, contains the corticosteroid triamcinolone acetonide . The spectrum of activity is broad and includes all fungal diseases of the skin caused by
- Dermatophytes : ( Trichophyton , Epidermophyton and Microsporum species)
- Yeast mushrooms : ( Candida species , Torulopsis , Rhodotorula , Malassezia furfur)
- Molds : ( Aspergillus , Cladosporium and Scopulariopsis brevicaulis species), as well as
- Secondary infections with gram-positive bacteria ( streptococci , staphylococci , Nocardia minutissima ).
Econazole is used to treat pityriasis versicolor ( synonym : bran fungus , bran ), a superficial yeast infection of the top layer of skin ( epidermis ) caused by Malassezia furfur . This fungus is often part of the normal skin flora . Increased fungal growth and symptoms of illness occur almost only in hyperhidrosis (excessive sweat production) as a disposition factor: tropics, hot and humid working atmosphere, sport, insufficient evaporation.
In gynecology , econazole is used in the form of creams, vaginal ovules or vaginal suppositories in the genital area to treat fungal infections of the vagina . A vaginal yeast infection is an infection of the vagina with yeast. Colloquially it is simply referred to as vaginal thrush and is almost always caused by the yeast Candida albicans or close relatives of the Candida genus . The disease is also called Soorkolpitis , Vaginalsoor or vulvovaginitis Candidomycetica (when the vulva referred to is also affected). Therapy with econazole is also indicated if there is also a secondary infection of the vagina with bacteria. In any case, the patient's sexual partner should also be treated in order to prevent reciprocal infection again ( “ping-pong effect” ).
Contraindications (contraindications)
The treatment with econazole is at a hypersensitivity to antifungals of the imidazole type, one of the pharmaceutical excipients and Präservativ- or Diaphragmagebrauch (Latex Products) contraindicated . Use on the eye or treating children with powder or pump spray is also not recommended; its effectiveness and safety have not been studied.
Use during pregnancy and breastfeeding
In animal experiments, econazole nitrate showed no teratogenic effects; in high doses it was foetotoxic. The informative value of these studies for humans is not known. In the gynecological use of econazole, the drug is absorbed through the vagina , it must not be used in the first trimester of pregnancy ; undesirable effects on the fruit in the womb during fetogenesis are possible. Vaginal dosage forms of econazole must not be used in the second and third trimesters.
It is not known whether econazole nitrate is excreted in human breast milk. If the patient is breastfeeding , vaginal application forms should be used with caution.
Adverse effects (side effects)
Local adverse effects that go beyond increased itching or burning are extremely rare (e.g. contact dermatitis ). When used in the genital area, irritation of the mucous membrane can occur (also in the patient's sexual partner) and latex condoms can be less tear-resistant. Due to the low level of absorption, no systemic side effects are known to date. The penetration of the skin layers allows adequate local therapy; supposed reservoirs, such as those in the gastrointestinal tract , remain unaffected.
Pharmacological properties
Mechanism of action (pharmacodynamics)
As an imidazole derivative, econazole has an antifungal effect by inhibiting the biosynthesis of ergosterol in fungi, which occurs via cytochrome P450 enzymes. They can also inhibit cytochrome P450-dependent monooxygenases in the cells of the human body. Above all, C14 demethylation is prevented during ergosterol synthesis. The enzyme responsible, 14 α -demethylase, is inhibited. It belongs to the fungus-specific cytochrome P450 isoenzymes ( CYP51A1 ). This main mechanism of action - the inhibition of the ergosterol synthesis - gives Econazole a very broad spectrum of activity.
Absorption and distribution in the body (pharmacokinetics)
After topical or vaginal use in humans, econazole is only slightly absorbed. Maximum plasma or serum concentrations of econazole and its metabolites are measured one to two days after application and reach approximately 20–40 ng · ml −1 for the cream . Econazole and the metabolites achieve a high systemic plasma protein binding of> 98%. The metabolism of econazole is done mostly by oxidation , deamination and O -Dealkylierung to metabolites which renal on or feces are excreted.
toxicology
To date, there have been no reports of overdose with econazole nitrate. In the event of accidental oral administration, vomiting , nausea and diarrhea may occur. If necessary, symptomatic treatment should be initiated and vital functions should be closely monitored.
The LD 50 value for oral administration is:
- Dog: 160 mg / kg
- Mouse: 462.7 mg / kg
- Rat: 667.7 mg / kg
- Guinea pigs: 272 mg / kg
Application in veterinary medicine
In veterinary medicine, econazole nitrate is used as an ointment (trade name: Epi-Pevaryl ® ) and used as an antimycotic for the topical treatment of dermatophytosis , local demodicosis and candidiasis, mycoplasmosis and against gram-positive bacteria. Usually the drug is applied twice a day. A special dosage is required for dermatomycosis in cats (topically up to 2–3 times a day) and in dogs (up to 2 times a day for 2–4 weeks).
chemistry
General information
Econazole is a synthetic imidazole derivative, its chemical structural formula is identical to that of miconazole except for one missing chlorine atom . It is used in all medicinal forms for topical application as econazole nitrate ( Latin : Econazoli nitras ) with the following chemical-physical properties: The name according to IUPAC nomenclature is: 1 - [(2 RS ) -2 - [(4-chlorobenzyl) oxy] -2- (2,4-dichlorophenyl) ethyl] -1 H -imidazole nitrate, the empirical formula is C 18 H 16 Cl 3 N 3 O 4 with a molar mass of 444.70 g · mol −1 . The melting point is 162 ° C (from a mixture of 2-propanol , methanol and diisopropyl ether ). Econazole nitrate is very sparingly soluble in water; soluble in methanol; sparingly soluble in ethanol ; slightly soluble in chloroform , dichloromethane ; very sparingly soluble to practically insoluble in diethyl ether . It is a white to almost white, crystalline or microcrystalline powder. The test for identity according to Ph. Eur. 5th edition, Grundwerk 2005 is carried out with the help of infrared spectroscopy and a subsequent comparison with the reference spectrum of econazole nitrate.
Stereochemistry
Econazole is a chiral drug with a stereocenter . (+) - Econazole is subject to racemization in vivo . The racemate, the 1: 1 mixture of the ( S ) and the ( R ) isomer, is used therapeutically .
Trade names
- Epi-Pevaryl (D)
- Gyno-Pevaryl (D, A, CH)
- Pevaryl (A, CH)
- Epipevisone (D)
- Pevisone (A, CH)
- Pevaryl cream (A)
Web links
- Entry on econazole nitrate in the ChemIDplus database of the United States National Library of Medicine (NLM)
literature
- Hermann J. Roth: Medicinal Chemistry: Targets and Drugs. Deutscher Apotheker Verlag, Stuttgart 2005, ISBN 3-7692-3483-9 .
- Gernot Rassner: Dermatology: Textbook and Atlas . Elsevier, Urban and Fischer Verlag, Munich / Jena 2007, ISBN 978-3-437-42762-6 .
- 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.
Individual evidence
- ↑ a b c d e Econazole nitrate salt data sheet from Sigma-Aldrich , accessed on March 29, 2011 ( PDF ).
- ↑ Tinea of the bare skin. ( Memento from January 19, 2010 in the Internet Archive ) Guidelines of the German Dermatological Society and the German-speaking Mycological Society.
- ↑ W. Forth, D. Henschler, W. Rummel: General and special pharmacology and toxicology . 9th edition. URBAN & FISCHER, Munich 2005, ISBN 3-437-42521-8 .
- ↑ Product information for the drug Gyno-Pevaryl ® Ovula / combination pack from Janssen-Cilag GmbH .
- ↑ entry to econazole in Vetpharm, accessed on 21 November 2011th
- ↑ Patent DE1940388 : New 1- (β-aryl) ethylimidazole derivatives, their preparation and use. Published February 26, 1970 , inventor: Erik Fred Godefroi.
- ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th Edition, Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 978-0-911910-00-1 .
- ↑ European Pharmacopoeia Commission (Ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006, pp. 2023-2024 .
- ↑ Christopher Pepper, H. John Smith, Kevin J. Barrell, Paul J. Nicholls, Michael JE Hewlins: Racemization of drug enantiomers by benzylic proton abstraction at physiological pH . In: Chirality . tape 6 , no. 5 , 1994, pp. 400-404 , doi : 10.1002 / chir.530060507 , PMID 8068499 .
- ↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) , Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10 -9 , p. 178.
