Alitretinoin
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| Non-proprietary name | Alitretinoin | ||||||||||||||||||
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| Molecular formula | C 20 H 28 O 2 | ||||||||||||||||||
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| Molar mass | 300.44 g mol −1 | ||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Alitretinoin is a drug selected from the group of retinoids , in the treatment of chronic hand eczema is used. It is a naturally occurring hormone and the isomerization product of all-trans - vitamin A acid.
Clinical information
application areas
Alitretinoin is used to treat chronic hand eczema and skin lesions in AIDS patients with Kaposi's sarcoma . In the form of Panretin, it is also used for the off-label use of cutaneous T-cell lymphomas , psoriasis and severe acne .
Drug interactions
Alitretinoin must not be used together with other topicals . DEET -containing insect repellants should not be used at the same time as alitretinoin, cytochrome P450 isoenzyme-inducing drugs can possibly reduce the alitretinoin level.
unwanted effects
The most common side effect is headache in 20% of all patients in the first 10 days after oral administration. Like all vitamin A derivatives, alitretinoin is a powerful teratogen . In addition, skin irritation with erythema , reddening, irritation, itching, scab and crust formation can occur with dermal application , as well as edema and blistering with continued treatment .
Pharmacological properties
Mechanism of action
Alitretinoin presumably acts on intracellular retinoid receptors of the subtypes RAR and RXR. The activated receptors act as transcription factors , which in turn have effects on cell proliferation and differentiation .
Alitretinoin acts on both keratinocytes and dendritic cells . Keratinocytes show a reduction in cytokine expression, while in dendritic cells the increase in expression of the maturation marker CD83 and the co-stimulatory factors CD80 and CD86 are inhibited. The dendritic cells influenced in this way show reduced T cell activating properties.
Absorption and distribution in the body
When taken orally, alitretinoin has a variable rate of absorption, improving absorption after ingestion. It is strongly bound to plasma proteins. Metabolism takes place in the liver via CYP3A4 , whereby 4-oxoalitretinoin is formed. The half-life is 2–10 hours and elimination takes place renally .
When applied dermally, there is no significant systemic distribution.
synthesis
Alitretinoin can be produced from all-trans -retinic acid by reaction over palladium catalysts:
Trade names
Monopreparations : Panretin (D), Toctino (D).
Web links
Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Alitretinoin
literature
- Thomas King, John McKenna, Anton B. Alexandroff: Alitretinoin for the treatment of severe chronic hand eczema . In: Patient preference and adherence . tape 8 , 2014, p. 1629–1634 , doi : 10.2147 / PPA.S38830 , PMID 25525339 , PMC 4270191 (free full text).
- Maureen A. Kane: Analysis, occurrence, and function of 9-cis-retinoic acid . In: Biochimica et Biophysica Acta . tape 1821 , no. 1 , 2012, p. 10-20 , doi : 10.1016 / j.bbalip.2011.09.012 .
- Pedram Ghasri, Noah Scheinfeld: Update on the use of alitretinoin in treating chronic hand eczema . In: Clinical, cosmetic and investigational dermatology . tape 3 , 2010, p. 59-65 , PMID 21437060 , PMC 3047954 (free full text).
- Caleb Cheng, Jason Michaels, Noah Scheinfeld: Alitretinoin: a comprehensive review . In: Expert Opinion on Investigational Drugs . tape 17 , no. 3 , 2008, p. 437-443 , doi : 10.1517 / 13543784.17.3.437 , PMID 18321241 .
Individual evidence
- ↑ a b c data sheet 9-cis-Retinoic acid from Sigma-Aldrich , accessed on June 26, 2017 ( PDF ).
- ↑ Kerstin A. Gräfe, Brigitte M. Gensthaler: Alitretinoin and Argatroban . In: Pharmaceutical newspaper . No. 35 , 2005 ( online ).
- ↑ a b entry on alitretinoin. In: Römpp Online . Georg Thieme Verlag, accessed on June 26, 2017.
- ↑ a b Andreas Katsambas, Torello Lotti, Clio Dessinioti, Angelo Massimiliano D'Erme (eds.): European Handbook of Dermatological Treatments . 3. Edition. Springer, Berlin / Heidelberg 2015, ISBN 978-3-662-45139-7 , pp. 353 ( limited preview in Google Book search).
- ↑ a b c d Drugs: Alitretinoin | Panretin®. In: Pharmaceutical Newspaper Online . February 25, 2016. Retrieved June 26, 2017 .
- ↑ Björn Lemmer , Kay Brune (eds.): Pharmacotherapy, clinical pharmacology . 14., revised. and updated edition. Springer, Heidelberg 2010, ISBN 978-3-642-10540-1 , pp. 425 .
- ^ A b Aditya Kumar Bubna: Alitretinoin in Dermatology — An Update . In: Indian Journal of Dermatology . tape 60 , no. 5 , 2015, p. 520 , doi : 10.4103 / 0019-5154.164426 , PMID 26538721 , PMC 4601442 (free full text).
- ↑ Andreas Kislat, Stephan Meller, Rodrigo Mota, Peter A. Gerber, Bettina A. Buhren, Erich Bünemann, Ulrike Wiesner, Thomas Ruzicka, Bernhard Homey: Alitretinoin - molecular and cellular mechanisms of action . In: Journal of Translational Medicine . tape 9 , Suppl 2, 2011, p. P16 , doi : 10.1186 / 1479-5876-9-S2-P16 , PMC 3242242 (free full text).
- ↑ Patent CN103058850 : Method for preparing alitretinoin. Published on April 24, 2013 , Inventors: Deng Qingjun, Wang Shaohui.
- ↑ ROTE LISTE 2017, Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-946057-10-9 , p. 159.
