Voriconazole
Structural formula | |||||||||||||||||||
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General | |||||||||||||||||||
Non-proprietary name | Voriconazole | ||||||||||||||||||
other names |
(2 R , 3 S ) -2- (2,4-difluorophenyl) -3- (5-fluoro-4-pyrimidinyl) -1- (1 H -1,2,4-triazol-1-yl) -2 -butanol |
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Molecular formula | C 16 H 14 F 3 N 5 O | ||||||||||||||||||
Brief description |
white solid |
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Drug information | |||||||||||||||||||
ATC code | |||||||||||||||||||
Drug class | |||||||||||||||||||
Mechanism of action |
Ergosterol synthesis inhibitors |
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properties | |||||||||||||||||||
Molar mass | 349.3 g · mol -1 | ||||||||||||||||||
Physical state |
firmly |
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Melting point |
127 ° C |
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solubility |
soluble in methanol |
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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 . |
Voriconazole (trade name VFend ; manufacturer: Pfizer ) is a drug used to treat patients with severe fungal infections ( mycoses ). Voriconazole is an inhibitor of ergosterol biosynthesis and belongs to the substance class of azole antimycotics.
Uptake and bioavailability
After oral administration, voriconazole has a bioavailability of approx. 96% of the applied dose. The maximum plasma concentration of voriconazole is reached 1 to 2 hours after administration.
The substance is offered as a powder for making a juice or a solution for infusion.
Metabolism (metabolism)
Voriconazole is metabolized in the liver by means of the cytochrome P450 enzymes CYP2C19, CYP2C9 and CYP3A4. The main metabolite of voriconazole is N -voriconazole oxide (72% of all voriconazole metabolites).
Interactions
- Carbamazepine
- Barbiturates such as phenobarbital , butalbital
- Rifampicin
- Sirolimus
- Terfenadine
- Astemizole
- Cisapride
- Ciclosporin
- Tacrolimus
- Anticoagulants such as phenprocoumon , warfarin, and coumarin
- Benzodiazepines ' like midazolam , alprazolam
- Calcium antagonists such as felodipine , nifedipine
- Rifabutin
- Phenytoin : Concomitant use of voriconazole and phenytoin lowers the C max and AUC of voriconazole by 50–70%. Similarly, phenytoin reduces the effect of voriconazole. Since voriconazole significantly increases the C max and AUC of phenytoin, regular phenytoin levels must be checked at shorter intervals than usual.
- Omeprazole : Concomitant use of omeprazole and voriconazole increases the AUC and maximal concentration (C max ) of voriconazole by approximately 15% and 40%, respectively. This leads to an increase in the effectiveness of voriconazole. However, dose adjustment (reduction) of voriconazole is not recommended. The C max and AUC of omeprazole are increased two-fold by voriconazole. If voriconazole treatment is to be started in patients on omeprazole therapy, the omeprazole dose should be halved (if> 40 mg / day).
application areas
Voriconazole is a 2nd generation azole with good and broad in-vitro activity against molds. It is used for severe systemic fungal infections ( mycoses ), especially invasive aspergillosis . Even otherwise therapy-resistant infections with the infectious agents Scedosporium spp. (especially Scedosporium apiospermium and Scedosporium prolificans) and Fusarium spp. including Fusarium solani are treated with voriconazole. According to Abele-Horn, voriconazole is not effective against zygomycetes .
Web links
- US package insert voriconazole ( Memento of July 5, 2010 in the Internet Archive ) (PDF; as of March 2008).
- Aspergillosis Current state of knowledge on diagnosis, therapy, environmental conditions (PDF file; 658 kB) ITA article from Austria; 2001
Individual evidence
- ↑ a b c Datasheet Voriconazole, ≥98% (HPLC) from Sigma-Aldrich , accessed on November 5, 2019 ( PDF ).
- ↑ a b The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1728, ISBN 978-0-911910-00-1 .
- ↑ Jörg Braun: Infectious Diseases. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 437-519, here: p. 518 ( voriconazole ).
- ^ 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. 272 and 285 f.