VORICONAZOLE, (±)-

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H14F3N5O
Molecular Weight	349.3105
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00582

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 Target	Pharmacology	Condition	Potency
Cytochrome P450 51 28 Target ID: CHEMBL1780 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Invasive aspergillosis 14 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf	Curative	Approved 8429	VFEND Approved Use use in the treatment of the fungal infections Launch Date 2003
Esophageal candidiasis 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf	Curative	Approved 8429	VFEND Approved Use use in the treatment of the fungal infections Launch Date 2003
Scedosporium apiospermum infection 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf	Curative	Approved 8429	VFEND Approved Use use in the treatment of the fungal infections Launch Date 2003
Fusarium spp. 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021466lbl.pdf	Curative	Approved 8429	VFEND Approved Use use in the treatment of the fungal infections Launch Date 2003

C_max

Value	Dose	Analyte	Population
3.13 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.31 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.03 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	3 mg/kg 2 times / day steady-state, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.77 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	4 mg/kg 2 times / day steady-state, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.74 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19933807	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
13.9 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	6 mg/kg single, intravenous dose: 6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12.4 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
13.7 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	3 mg/kg 2 times / day steady-state, intravenous dose: 3 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
33.9 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	4 mg/kg 2 times / day steady-state, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
34 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.31 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
27.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19933807	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VORICONAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
15.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19933807	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VORICONAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
42% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021266s039,021267s050,021630s029lbl.pdf	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VORICONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and allergic bronchopulmonary aspergillosis Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	Disc. AE: Photophobia, Fatigue... AEs leading to discontinuation/dose reduction: Photophobia (1 patient) Fatigue (1 patient) Concentration impaired (1 patient) Insomnia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/
200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	Disc. AE: Function liver abnormal, Hallucination, visual... AEs leading to discontinuation/dose reduction: Function liver abnormal (73 patients) Hallucination, visual (16 patients) Skin rash (6 patients) Kidney dysfunction (3 patients) Electrocardiogram QTc interval prolonged (2 patients) Gastrointestinal symptom NOS (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/	unhealthy, 53.4–67.5 years n = 31 Health Status: unhealthy Condition: Acute myeloid leukemia, Acute lymphoid leukemia, Lymphoma, Others Age Group: 53.4–67.5 years Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/	Disc. AE: CRP increased, Bilirubin increased... AEs leading to discontinuation/dose reduction: CRP increased (31 patient) Bilirubin increased (31 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/
16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 9 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and invasive aspergillosis Age Group: 9 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	Disc. AE: Photophobia... AEs leading to discontinuation/dose reduction: Photophobia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/

AEs

AE	Significance	Dose	Population
Concentration impaired	1 patient Disc. AE	16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and allergic bronchopulmonary aspergillosis Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/
Fatigue	1 patient Disc. AE	16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and allergic bronchopulmonary aspergillosis Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/
Insomnia	1 patient Disc. AE	16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and allergic bronchopulmonary aspergillosis Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/
Photophobia	1 patient Disc. AE	16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 17 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and allergic bronchopulmonary aspergillosis Age Group: 17 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/
Gastrointestinal symptom NOS	1 patient Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Hallucination, visual	16 patients Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Electrocardiogram QTc interval prolonged	2 patients Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Kidney dysfunction	3 patients Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Skin rash	6 patients Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Function liver abnormal	73 patients Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/	unhealthy, 42.7–64.5 years n = 327 Health Status: unhealthy Condition: Acute myeloid leukemia, lymphocytic leukemia, Myelodysplastic syndrome, Multiple myeloma Lymphoma and Other Age Group: 42.7–64.5 years Sex: M+F Population Size: 327 Sources: https://pubmed.ncbi.nlm.nih.gov/32171012/
Bilirubin increased	31 patient Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/	unhealthy, 53.4–67.5 years n = 31 Health Status: unhealthy Condition: Acute myeloid leukemia, Acute lymphoid leukemia, Lymphoma, Others Age Group: 53.4–67.5 years Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/
CRP increased	31 patient Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/	unhealthy, 53.4–67.5 years n = 31 Health Status: unhealthy Condition: Acute myeloid leukemia, Acute lymphoid leukemia, Lymphoma, Others Age Group: 53.4–67.5 years Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/30306637/
Photophobia	1 patient Disc. AE	16 mg/kg 1 times / day steady, oral Recommended Dose: 16 mg/kg, 1 times / day Route: oral Route: steady Dose: 16 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/	unhealthy, 9 years n = 1 Health Status: unhealthy Condition: cystic fibrosis and invasive aspergillosis Age Group: 9 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/27313918/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 P-gp 1461 BCRP 699 BSEP 402 UGT2B 3	CYP2C19 991 CYP1A2 1054 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
UGT2B 3	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23653047/ Page: 17.0	likely
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17518356/	no
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/27001813/	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12, 13, 14	yes [Ki 14 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12, 13, 14	yes [Ki 22 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12, 13, 14	yes [Ki 7 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23084335/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021630s000_Vfend_ClinPharm.pdf Page: 2, 10,13, 21-23, 26-27	major	yes (co-administration study) Comment: from FDA label pp26-28: rifampin decreased voriconazole Cmax by 93% and AUC by 96% and fluconazole increased voriconazole Cmax by 57% and AUC 79% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021630s000_Vfend_ClinPharm.pdf Page: 2, 10,13, 21-23, 26-27
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 12.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 11.0	yes [Km 21 uM]	yes (co-administration study) Comment: from FDA label pp26-28: rifampin decreased voriconazole Cmax by 93% and AUC by 96%; fluconazole increased voriconazole Cmax by 57% and AUC 79% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 11.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 11.0	yes [Km 240 uM]	yes (co-administration study) Comment: from FDA label pp26-28: rifampin decreased voriconazole Cmax by 93% and AUC by 96%; fluconazole increased voriconazole Cmax by 57% and AUC 79% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-266_VFEND_biopharmr.pdf Page: 11.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:10023	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:10023
ChemicalBook	CB01123117	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01123117
ChemicalBook	CB1160110	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1160110
MolPort	MolPort-003-850-863	https://www.molport.com/shop/molecule-link/MolPort-003-850-863
Selleck Chemicals	Voriconazole	http://www.selleckchem.com/products/Voriconazole.html
ZINC	ZINC000000014864	http://zinc15.docking.org/substances/ZINC000000014864
eMolecules	30100386	https://www.emolecules.com/cgi-bin/more?vid=30100386
eMolecules	30487979	https://www.emolecules.com/cgi-bin/more?vid=30487979
eMolecules	902682	https://www.emolecules.com/cgi-bin/more?vid=902682

PubMed

Title	Date	PubMed
Antifungal activity of a new triazole, voriconazole (UK-109496), against clinical isolates of Aspergillus spp.	2000 Jun	11810544
[Therapy of invasive organ mycoses in patients with systemic hematologic diseases].	2001	11789423
Sputum isolation of Wangiella dermatitidis in patients with cystic fibrosis.	2001	11728050
Sporothrix schenckii sensitivity to voriconazole, itraconazole and amphotericin B.	2001 Aug	11556767
Application of capillary zone electrophoresis with off-line solid-phase extraction to in vitro metabolism studies of antifungals.	2001 Aug	11519954
Investigational antifungal agents.	2001 Aug	11501989
[Infection and colonization by Scedosporium prolificans].	2001 Aug-Sep	11747789
Aspergillus: rising frequency of clinical isolation and continued susceptibility to antifungal agents, 1994-1999.	2001 Dec	11777662
In vitro susceptibility of clinical isolates of Zygomycota to amphotericin B, flucytosine, itraconazole and voriconazole.	2001 Dec	11733480
Antifungal activity of the new azole UK-109 496 (voriconazole): addition and clarification.	2001 Nov	11766113
Muco-cutaneous retinoid-effects and facial erythema related to the novel triazole antifungal agent voriconazole.	2001 Nov	11722447
Effect of the growth medium on the in vitro antifungal activity of micafungin (FK-463) against clinical isolates of Candida dubliniensis.	2001 Nov	11679561
A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients.	2001 Nov 1	11577374
Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease.	2001 Nov 23	11698718
Update on antifungal agents.	2001 Oct	11642635
Antifungals: what's in the pipeline.	2001 Oct	11587930
Successful treatment of Candida glabrata myocarditis with voriconazole.	2002	12477337
Voriconazole: in the treatment of invasive aspergillosis.	2002	12466006
Successful treatment of Paecilomyces lilacinus endophthalmitis with voriconazole.	2002	12374371
Influence of voriconazole and fluconazole on Candida albicans in long-time continuous flow culture.	2002	12073562
Gateways to Clinical Trials.	2002 Apr	12087878
Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients.	2002 Apr	11999005
Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000.	2002 Apr	11897586
Case Reports. Chronic and acute Aspergillus meningitis.	2002 Dec	12472730
Effect of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on polymorphonuclear neutrophils, monocytes or monocyte-derived macrophages combined with voriconazole against Cryptococcus neoformans.	2002 Feb	11860010
Azole cross-resistance in Aspergillus fumigatus.	2002 Feb	11796377
A multidrug, including voriconazole, resistant oral Candida infection in an AIDS patient effectively treated with echinocandin.	2002 Jan	11972427
Voriconazole versus liposomal amphotericin B in patients with neutropenia and persistent fever.	2002 Jan 24	11807157
Empirical antifungal therapy--new options, new tradeoffs.	2002 Jan 24	11807153
Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever.	2002 Jan 24	11807146
Voriconazole and fluconazole susceptibility of Candida isolates.	2002 Jun	12018654
New drugs, old drugs - dear drugs, cheap drugs.	2002 Jun 15	12362279
Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children.	2002 Mar	12005089
Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis.	2002 Mar 1	11807679
Broth medium for microdilution susceptibility tests of fluconazole and voriconazole.	2002 May	12072930
Hypercalcemia induced by 13-cis-retinoic acid in a patient with neuroblastoma.	2002 May	12013365
Voriconazole versus liposomal amphotericin B for empirical antifungal therapy.	2002 May 30	12041527
Voriconazole versus liposomal amphotericin B for empirical antifungal therapy.	2002 May 30	12041526
Voriconazole -- better chances for patients with invasive mycoses.	2002 May 31	12069915
Management of mycoses in surgical patients -- review of the literature.	2002 May 31	12069912
Decisions about voriconazole versus liposomal amphotericin B.	2002 May 9	12000825
Gateways to clinical trials.	2002 Nov	12616707
In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592).	2002 Nov	12421285
The safety of voriconazole.	2002 Nov 15	12410490
Pseudallescheria boydii (Anamorph Scedosporium apiospermum). Infection in solid organ transplant recipients in a tertiary medical center and review of the literature.	2002 Sep	12352630
Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine.	2003 Feb	12627286
In vitro activity of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B against aspergillus spp.	2003 Feb	12614985
Disseminated infection due to Cylindrocarpon (Fusarium) lichenicola in a neutropenic patient with acute leukaemia: report of a case and review of the literature.	2003 Jan	12582748
Activity of voriconazole against corneal isolates of Scedosporium apiospermum.	2003 Jan	12502945
Voriconazole: a new triazole antifungal agent.	2003 Mar 1	12594645

Patents

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

Name

Type

Language

VORICONAZOLE, (±)-

Common Name

English

4-PYRIMIDINEETHANOL, .ALPHA.-(2,4-DIFLUOROPHENYL)-5-FLUORO-.BETA.-METHYL-.ALPHA.-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-, (.ALPHA.R,.BETA.S)-REL-

Systematic Name

English

(±)-VORICONAZOLE

Common Name

English

VORICONAZOLE RELATED COMPOUND A [USP IMPURITY]

Common Name

English

VORICONAZOLE RELATED COMPOUND A

Common Name

English

VORICONAZOLE RELATED COMPOUND A [USP-RS]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID201019420