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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H14F3N5O
Molecular Weight 349.3105
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VORICONAZOLE

SMILES

C[C@@H](C1=C(F)C=NC=N1)[C@](O)(CN2C=NC=N2)C3=C(F)C=C(F)C=C3

InChI

InChIKey=BCEHBSKCWLPMDN-MGPLVRAMSA-N
InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16+/m0/s1

HIDE SMILES / InChI

Description

Voriconazole (vor-i-KON-a-zole, brand name Vfend, Pfizer) is a triazole antifungal medication. VFEND® (voriconazole) is available as film-coated tablets for oral administration, and as a lyophilized powder for solution for intravenous infusion. 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. The primary mode of action of voriconazole is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of voriconazole. Voriconazole has been shown to be more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems. The most common side effects associated with voriconazole include transient visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, and respiratory disorder. Unlike most adverse effects, which are similar to other azole antifungal agents, visual disturbances (such as blurred vision or increased sensitivity to light) are unique to voriconazole. Though rare, there have been cases of serious hepatic reactions during treatment with voriconazole (a class effect of azole antifungal agents). Liver function tests should be evaluated at the start of and during the course of therapy. Voriconazole is phototoxic. It has been associated with an increased risk of squamous-cell carcinoma of the skin

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
VFEND
Curative
VFEND
Curative
VFEND
Curative
VFEND

Cmax

ValueDoseCo-administeredAnalytePopulation
3.13 μg/mL
6 mg/kg single, intravenous
VORICONAZOLE plasma
Homo sapiens
2.31 μg/mL
200 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens
3.03 μg/mL
3 mg/kg 2 times / day steady-state, intravenous
VORICONAZOLE plasma
Homo sapiens
4.77 μg/mL
4 mg/kg 2 times / day steady-state, intravenous
VORICONAZOLE plasma
Homo sapiens
4.74 μg/mL
300 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens
2.3 μg/mL
400 mg single, oral
VORICONAZOLE plasma
Homo sapiens
3.1 μg/mL
200 mg 2 times / day steady-state, oral
VORICONAZOLE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13.9 μg × h/mL
6 mg/kg single, intravenous
VORICONAZOLE plasma
Homo sapiens
12.4 μg × h/mL
200 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens
13.7 μg × h/mL
3 mg/kg 2 times / day steady-state, intravenous
VORICONAZOLE plasma
Homo sapiens
33.9 μg × h/mL
4 mg/kg 2 times / day steady-state, intravenous
VORICONAZOLE plasma
Homo sapiens
34 μg × h/mL
300 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens
9.31 μg × h/mL
400 mg single, oral
VORICONAZOLE plasma
Homo sapiens
27.9 μg × h/mL
200 mg 2 times / day steady-state, oral
VORICONAZOLE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
15.5 h
200 mg 2 times / day steady-state, oral
VORICONAZOLE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
42%
200 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens
42%
300 mg 2 times / day multiple, oral
VORICONAZOLE plasma
Homo sapiens

Doses

AEs

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Tablets should be taken at least one hour before, or one hour following, a meal.
Route of Administration: Oral
In Vitro Use Guide
each microdilution well containing 100 ul of the drug concentrations was inoculated with 100 ul of the diluted inoculum suspension (final volume in each well was 200 ul). Drug concentrations were 0.03 to 16 mg/ml for voriconazole. Stock inoculum suspensions of the molds were prepared from 7-day (Aspergillus spp., Bipolaris spp., P. boydii, R. arrhizus, and S. schenckii) or 7- to 10-day (B. dermatitidis and H. capsulatum) cultures grown on PDA at 35°C (cultures for Fusarium spp. were grown at 35°C for 48 to 72 h and then at 25 to 28°C until day 7