Name: | voriconazole |
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PubChem Compound ID: | 5231054 |
Molecular formula: | C16H14F3N5O |
Molecular weight: | 349.311 g/mol |
Name: | voriconazole |
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Name (isomeric): | DB00582 |
Drug Type: | small molecule |
Synonyms: |
VCZ
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Brand: | Vfend |
Category: | Antifungal Agents, Antifungals |
CAS number: | 137234-62-9 |
Indication: | For the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by <i>Scedosporium apiospermum</i> and <i>Fusarium</i> spp. |
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Pharmacology: |
Voriconazole is a triazole antifungal agent indicated for use in the treatment of fungal infections including invasive aspergillosis, esophageal candidiasis, and serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani. Fungal plasm...
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Voriconazole is a triazole antifungal agent indicated for use in the treatment of fungal infections including invasive aspergillosis, esophageal candidiasis, and serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani. Fungal plasma membranes are similar to mammalian plasma membranes, differing in having the nonpolar sterol ergosterol, rather than cholesterol, as the principal sterol. Membrane sterols such as ergosterol provide structure, modulation of membrane fluidity, and possibly control of some physiologic events. Voriconazole effects the formation of the fungal plasma membrane by indirectly inhibiting the biosynthesis of ergosterol. This results in plasma membrane permeability changes and inhibition of growth.
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Mechanism of Action: | Voriconazole binds and inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-alpha sterol demethylase. The inhibition of 14-alpha sterol demethylase results in a depletion of ergosterol in fungal cell membrane. |
Absorption: | The oral bioavailability is estimated to be 96% (CV 13%). |
Protein binding: | 58% |
Biotransformation: | Hepatic. The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma. Since this metabolite has minimal antifungal activity, it does not contribute to the overall efficacy of voriconazole. |
Route of elimination: | Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine. |
Toxicity: | The minimum lethal oral dose in mice and rats was 300 mg/kg (equivalent to 4 and 7 times the recommended maintenance dose (RMD), based on body surface area). At this dose, clinical signs observed in both mice and rats included salivation, mydriasis, titubation (loss of balance while moving), depressed behavior, prostration, partially closed eyes, and dyspnea. Other signs in mice were convulsions, corneal opacification and swollen abdomen. |
Affected organisms: | Yeast and other fungi |
Drug interaction: |
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UniProt ID: | P10613 | |||||||||
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Gene: | ERG11 | |||||||||
Actions: | antagonist, inhibitor | |||||||||
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UniProt ID: | Q01740 | |
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Gene: | FMO1 | |
Actions: | substrate | |
References: |
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UniProt ID: | P31513 | |
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Gene: | FMO3 | |
Actions: | substrate | |
References: |
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UniProt ID: | P20815 | |
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Gene: | CYP3A5 | |
Actions: | inhibitor | |
References: |
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UniProt ID: | P24462 | |
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Gene: | CYP3A7 | |
Actions: | inhibitor | |
References: |
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UniProt ID: | P33261 | ||
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Gene: | CYP2C19 | ||
Actions: | substrate, inhibitor | ||
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UniProt ID: | P08684 | |||
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Gene: | CYP3A4 | |||
Actions: | substrate, inhibitor | |||
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UniProt ID: | P11712 | |||
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Gene: | CYP2C9 | |||
Actions: | substrate, inhibitor | |||
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UniProt ID: | P23219 | |
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Gene: | PTGS1 | |
Actions: | substrate | |
References: |
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