U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C23H32N6O4S.ClH.3H2O
Molecular Weight 579.1117
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VARDENAFIL HYDROCHLORIDE

SMILES

CCCc1nc(C)c2c(=O)nc(-c3cc(ccc3OCC)S(=O)(=O)N4CCN(CC)CC4)[nH]n12.Cl.O.O.O

InChI

InChIKey=FBCDRHDULQYRTB-UHFFFAOYSA-N
InChI=1S/C23H32N6O4S.ClH.3H2O/c1-5-8-20-24-16(4)21-23(30)25-22(26-29(20)21)18-15-17(9-10-19(18)33-7-3)34(31,32)28-13-11-27(6-2)12-14-28;;;;/h9-10,15H,5-8,11-14H2,1-4H3,(H,25,26,30);1H;3*1H2

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C23H32N6O4S
Molecular Weight 488.605
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021400s017lbl.pdf

Vardenafil (Levitra) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.

CNS Activity

Curator's Comment:: Vardenafil crossed the BBB

Originator

Curator's Comment:: # Bayer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Levitra

Approved Use

LEVITRA is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.

Launch Date

1061164800000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
30.1 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
22.83 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.21 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2.4 mg 12 times / day multiple, respiratory
Highest studied dose
Dose: 2.4 mg, 12 times / day
Route: respiratory
Route: multiple
Dose: 2.4 mg, 12 times / day
Sources:
healthy, 27.5 years (range: 24-31 years)
Health Status: healthy
Age Group: 27.5 years (range: 24-31 years)
Sex: M+F
Sources:
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Other AEs: Back pain, Myalgia...
Other AEs:
Back pain
Myalgia
Abnormal vision
Sources:
2.4 mg single, respiratory
Highest studied dose
Dose: 2.4 mg
Route: respiratory
Route: single
Dose: 2.4 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M+F
Sources:
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Headache, Flushing...
AEs leading to
discontinuation/dose reduction:
Headache (19 patients)
Flushing (10 patients)
Rhinitis (5 patients)
Tachycardia (4 patients)
Nausea (5 patients)
Liver function test abnormal (4 patients)
Dizziness (3 patients)
Hypesthesia (3 patients)
Abdominal pain (3 patients)
Palpitations (3 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abnormal vision
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Back pain
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Myalgia
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Flushing 10 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Headache 19 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Abdominal pain 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Dizziness 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Hypesthesia 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Palpitations 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Liver function test abnormal 4 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Tachycardia 4 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Nausea 5 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Rhinitis 5 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Overview

OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: label: coadministration with ketoconazole (inhibitor) increased mean AUC and Cmax of vardenafil by 10-fold and 4-fold, respectively; coadministration with erythromycin (CYP3A4 substrate) increased mean AUC and Cmax of vardenafil, respectively; coadministration with indinavir (CYP3A4 inhibitor) increased mean AUC and Cmax of vardenafil by 16 fold and 7 fold, respectively; Ritonavir co-administered with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13­ fold increase in vardenafil Cmax;
Page: 19
minor
minor
minor
minor
yes
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Vardenafil increases penile rigidity and tumescence in men with erectile dysfunction after a single oral dose.
2001 Aug
Towards optimal ED management: educational forum - II.
2001 Dec
Current treatments and emerging therapeutic approaches in male erectile dysfunction.
2001 Oct
Inhibition of cyclic GMP hydrolysis in human corpus cavernosum smooth muscle cells by vardenafil, a novel, selective phosphodiesterase type 5 inhibitor.
2001 Sep 28
PDE-5 inhibition and sexual response: pharmacological mechanisms and clinical outcomes.
2002
Vardenafil: update on clinical experience.
2002 Feb
[Therapy of erectile dysfunction. New, highly selective PDE-5 inhibitor].
2002 Feb 14
[Erectile dysfunction. New therapy options ante portas].
2002 Feb 14
Pharmacology of phosphodiesterase-5 inhibitors.
2002 Jul-Aug
Gateways to clinical trials.
2002 May
Tadalafil (Cialis) for men with erectile dysfunction.
2002 May
Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil--review of the literature.
2002 Oct 29
Gateways to Clinical Trials.
2002 Sep
Erectile dysfunction: oral pharmacotherapy options.
2002 Sep
Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial.
2003 Apr
Hypogonadism and erectile dysfunction: the role for testosterone therapy.
2003 Aug
Erectile dysfunction in the cardiac patient: how common and should we treat?
2003 Aug
US advertising campaign begins for alternative to sildenafil.
2003 Aug 30
Molecular mechanisms and pharmacokinetics of phosphodiesterase-5 antagonists.
2003 Dec
Effective treatment of erectile dysfunction with vardenafil.
2003 Jan
New phosphodiesterase type 5 inhibitors in the management of erectile dysfunction.
2003 Jun
Proceedings of the 99th meeting of the Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee. May 29th and 30th, 2003.
2003 Jun 17
[New PDE-5 inhibitor for treatment of impotence. 9 out of 10 have erections again].
2003 Jun 26
Gateways to clinical trials. March 2003.
2003 Mar
Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study.
2003 Mar
Switching patients with erectile dysfunction from sildenafil citrate to tadalafil: results of a European multicenter, open-label study of patient preference.
2003 Nov
New tools 2003.
2003 Nov-Dec
[Drug therapy of erectile dysfunction--the current status].
2003 Oct
Phosphodiesterase type 5 inhibitors: a biochemical and clinical correlation survey.
2003 Oct
Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.
2003 Oct
New drugs and dosage forms.
2003 Oct 1
[Medication of the month. Vardenafil (Levitra)].
2003 Sep
Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups.
2003 Sep
Phosphodiesterase 5 inhibitors in male sexual dysfunction.
2003 Sep
Vardenafil (levitra) for erectile dysfunction.
2003 Sep 29
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.
2003 Sep 4
Novel phosphodiesterase type 5 inhibitors: assessing hemodynamic effects and safety parameters.
2004 Apr
Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles.
2004 Apr
Role of the cardiologist: clinical aspects of managing erectile dysfunction.
2004 Apr
Pills for erectile dysfunction: now there are three.
2004 Apr
Treatment of erectile dysfunction.
2004 Apr
Erectile dysfunction: management update.
2004 Apr 27
Tadalafil (Cialis) and vardenafil (Levitra) recently approved drugs for erectile dysfunction.
2004 Feb
[Erectile dysfunction. Epidemiology, physiology, etiology, diagnosis and therapy].
2004 Feb
Drug approval highlights for 2003.
2004 Feb
Cardioprotection with phosphodiesterase-5 inhibition--a novel preconditioning strategy.
2004 Feb
[Treatment of erectile dysfunction].
2004 Feb 29
Pharmacokinetics, pharmacodynamics, and efficacy of phosphodiesterase type 5 inhibitors.
2004 Mar
Therapeutic options for patients returning to sexual activity.
2004 Mar
The efficacy and safety of flexible-dose vardenafil (levitra) in a broad population of European men.
2004 May
Patents

Sample Use Guides

For most patients, the starting dose is 10 mg, up to once daily. Increase to 20 mg or decrease to 5 mg based on efficacy/tolerability.
Route of Administration: Oral
Treatment with vardenafil at concentrations of 50, 100, and 250 umol/L increased expression of PlGF in a dose-dependent manner in human umbilical vein endothelial cells.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:06:49 UTC 2021
Edited
by admin
on Fri Jun 25 21:06:49 UTC 2021
Record UNII
5M8S2CU0TS
Record Status Validated (UNII)
Record Version
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Name Type Language
VARDENAFIL HYDROCHLORIDE
ORANGE BOOK   USP-RS   WHO-DD  
Common Name English
VARDENAFIL HYDROCHLORIDE TRIHYDRATE
MI  
Preferred Name English
VARDENAFIL HYDROCHLORIDE HYDRATE [JAN]
Common Name English
VARDENAFIL HCL
Common Name English
VARDENAFIL HYDROCHLORIDE [USP-RS]
Common Name English
NUVIVA
Brand Name English
PIPERAZINE, 1-((3-(1,4-DIHYDRO-5-METHYL-4-OXO-7-PROPYLIMIDAZO(5,1-F)(1,2,4)TRIAZIN-2-YL)-4-ETHOXYPHENYL)SULFONYL)-4-ETHYL-, MONOHYDROCHLORIDE, TRIHYDRATE
Systematic Name English
BAY-38-9456
Code English
VARDENAFIL HYDROCHLORIDE TRIHYDRATE [EP MONOGRAPH]
Common Name English
VARDENAFIL HYDROCHLORIDE HYDRATE
JAN  
Common Name English
VARDENAFIL HYDROCHLORIDE [WHO-DD]
Common Name English
IMIDAZO(5,1-F)(1,2,4)TRIAZIN-4(1H)-ONE, 2-(2-ETHOXY-5-((4-ETHYL-1-PIPERAZINYL)SULFONYL)PHENYL)-5-METHYL-7-PROPYL-, HYDROCHLORIDE, HYDRATE (1:1:3)
Systematic Name English
BAY 38-9456
Code English
2-(2-ETHOXY-5-(4-ETHYL-PIPERAZINE-1-SULFONYL)-PHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZO(5,1-F)(1,2,4)TRIAZIN-4-ONE, HYDROCHLORIDE TRIHYDRATE
Systematic Name English
STAXYN
Brand Name English
VARDENAFIL HYDROCHLORIDE TRIHYDRATE [MI]
Common Name English
VARDENAFIL HYDROCHLORIDE TRIHYDRATE [WHO-DD]
Common Name English
VARDENAFIL HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
VARDENAFIL HYDROCHLORIDE [ORANGE BOOK]
Common Name English
LEVITRA
Brand Name English
PIPERAZINE, 1-((3-(1,4-DIHYDRO-5-METHYL-4-OXO-7-PROPYLIMIDAZO(5,1-F)(1,2,4)TRIAZIN-2-YL)-4-ETHOXYPHENYL)SULFONYL)-4-ETHYL-, MONOHYDROCHLORIDE TRIHYDRATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2127
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
Code System Code Type Description
DRUG BANK
DBSALT001741
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
RXCUI
1309396
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
ALTERNATIVE
MERCK INDEX
M11394
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
FDA UNII
5M8S2CU0TS
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
CAS
330808-88-3
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
USP_CATALOG
1711010
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY USP-RS
PUBCHEM
135413545
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
EVMPD
SUB20775
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
NCI_THESAURUS
C76318
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL1520
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
EVMPD
SUB23180
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
RXCUI
307306
Created by admin on Fri Jun 25 21:06:49 UTC 2021 , Edited by admin on Fri Jun 25 21:06:49 UTC 2021
PRIMARY
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