(2S,3R)-2-(2,4-ジフルオロフェニル)-3-(5-フルオロピリミジン-4-イル)-1-(1H-1,2,4-トリアゾール-1-イル)ブタン-2-オール

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Anti infectives for systemic use -> Antibacterials for systemic use

1

1.7

Low

9.78e-02 g/L

Breast Feeding; Lactation; Milk, Human; Antifungal Agents

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Danger

H301 (99.2%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P260, P264, P270, P273, P280, P301+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 118 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Transient elevations in serum aminotransferase levels occur in 11% to 19% of patients on voriconazole. These elevations are usually asymptomatic and self-limited, but approximately 1% of patients require discontinuation of voriconazole because of ALT elevations. Clinically apparent hepatotoxicity is uncommon, but may be more frequent than with fluconazole and itraconazole. The injury arises within the first month of therapy and the pattern of serum enzyme elevations has been variable from cholestatic to hepatocellular. Several cases of acute liver failure attributed to voriconazole have been reported. Immunoallergic features and autoantibodies are uncommon. Recovery upon stopping therapy generally takes 6 to 10 weeks but, in some cases, the time to complete resolution may be prolonged.

Voriconazole

Group 1: Carcinogenic to humans

Volume 137: (2026) Hydrochlorothiazide, Voriconazole, and Tacrolimus

2026 online

2024

Drug Induced Liver Injury Rank (DILIrank 2.0)

Voriconazole

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

J02AC03

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J02AC03

Voriconazole is used to treat fungal infections caused by a variety of organisms but including _Aspergillus spp._ and _Candida spp_. Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens. Like other triazoles, voriconazole binds to 14-alpha sterol demethylase, also known as CYP51, and inhibits the demethylation of lanosterol as part of the ergosterol synthesis pathway in yeast and other fungi. The lack of sufficient ergosterol disrupts fungal cell membrane function and limits fungal cell growth. With fungal growth limited, the host's immune system is able to clear the invading organism.

Voriconazole undergoes extensive hepatic metabolism through cytochrome enzymes CYP2C9, CYP2C19, and CYP3A4. CYP2C19 mediates N-oxidation with an apparent Km of 14 μM and an apparent Vmax of 0.22 nmol/min/nmol CYP2C19. Voriconazole N-oxide is the major circulating metabolite, accounting for 72% of radiolabeled metabolites found. CYP3A4 contributes to N-oxidation with a Km of 16 μM and Vmax of 0.05 nmol/min/nmol CYP3A4 as well as 4-hydroxylation with a Km of 11 μM and a Vmax of 0.10 nmol/min/nmol CYP3A4. CYP3A5 and CYP3A7 provide minor contributions to N-oxidation and 4-hydroxylation. The N-oxide and 4-hydroxylated metabolites undergo glucuronidation and are excreted through the urine with other minor glucuronidated metabolites.

Voriconazole has known human metabolites that include Voriconazole N-Oxide and Hydroxymethyl Voriconazole.

JFU09I87TR

VORICONAZOLE

Established Pharmacologic Class [EPC] - Azole Antifungal

Chemical Structure [CS] - Azoles

Mechanisms of Action [MoA] - Cytochrome P450 3A4 Inhibitors

Mechanisms of Action [MoA] - Cytochrome P450 2C19 Inhibitors

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.

Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A.

The oral bioavailability is estimated to be 96% in healthy adults. Population pharmacokinetic studies report a reduced bioavailability pediatric patients with a mean of 61.8% (range 44.6–64.5%) thought to be due to differences in first-pass metabolism or due to differences in diet. Of note, transplant patients also have reduced bioavailability but this is known to increase with time after transplantation and may be due in part to gastrointestinal upset from surgery and some transplant medications. Tmax is 1-2 hours with oral administration. When administered with a high-fat meal Cmax decreases by 34% and AUC by 24%. pH does not have an effect on absorption of voriconazole. Differences in Cmax and AUC have been observed between healthy adult males and females with Cmax increasing by 83% and AUC by 113% although this has not been observed to significantly impact medication safety profiles.

Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.

The estimated volume of distribution of voriconazole is 4.6 L/kg. Population pharmacokinetic studies estimate the median volume of distribution to be 77.6 L with the central compartment estimated at 1.07 L/kg Voriconazole is known to achieve therapeutic concentrations in many tissues including the brain, lungs, liver, spleen, kidneys, and heart.

The clearance of voriconazole is estimated to be a mean of 5.25-7 L/h in healthy adults for the linear portion of the drug's kinetics.