Vardenafil

Identification

Summary

Vardenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction.

Brand Names
Levitra, Staxyn
Generic Name
Vardenafil
DrugBank Accession Number
DB00862
Background

Vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) and an oral therapy for the treatment of erectile dysfunction.5,6 During sexual stimulation, nitric oxide (NO) is released from nerve endings and endothelial cells in the corpus cavernosum, activating the enzyme guanylate cyclase and increasing the synthesis of cGMP in the smooth muscle cells of the corpus cavernosum. PDE5 inhibitors, such as vardenafil, inhibit the degradation of cGMP and allow increased blood flow into the penis, resulting in an erection.1,5,6. Compared to sildenafil and tadalafil, vardenafil is a more potent inhibitor of PDE5; however, its selectivity for other PDE isoforms is lower than the one detected for tadalafil.4

The FDA approved the use of vardenafil for the treatment of erectile dysfunction in 2003. Although other PDE5 inhibitors such as sildenafil and tadalafil have been associated with rare cases of acute liver injury, the use of vardenafil has not been linked to hepatotoxic effects.3 The use of vardenafil as a monotherapy for the treatment of pulmonary arterial hypertension has also been evaluated.2

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 488.603
Monoisotopic: 488.220574232
Chemical Formula
C23H32N6O4S
Synonyms
  • Vardénafil
  • Vardenafil
  • Vardenafilo
  • Vardenafilum
External IDs
  • BAY 389456
  • BAY-389456
  • BAY38-9456
  • DE 19750085 1997
  • WO 99/24433 1999

Pharmacology

Indication

Vardenafil is indicated for the treatment of erectile dysfunction.5,6,7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofErectile dysfunction••••••••••••••••••• ••••••• •••••• ••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Vardenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), an enzyme responsible for the degradation of cGMP in the corpus cavernosum. The presence of cGMP in the corpus cavernosum leads to smooth muscle relaxation, an increased inflow of blood and an erection. Therefore, in patients with erectile dysfunction given vardenafil, normal sexual stimulation will increase cGMP levels in the corpus cavernosum. Without sexual stimulation and no cGMP production, vardenafil should not cause an erection.5,6

Vardenafil should not be used in men for whom sexual activity is not recommended due to their underlying cardiovascular status. There is also a risk of developing prolonged erections that last longer than 4 hours, as well as priapism. In the event of a sudden loss of vision in one or both eyes, patients should stop using vardenafil. Patients taking PDE5 inhibitors, such as vardenafil, may also develop sudden hearing loss and experience a prolonged QT interval.5,6

Mechanism of action

Vardenafil inhibits cyclic guanosine monophosphate (GMP) specific phosphodiesterase type 5 (PDE5), which is responsible for the degradation of cyclic GMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cyclic GMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The tissue concentration of cyclic GMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs), and the most abundant PDE in the human corpus cavernosum is PDE5. Therefore, the inhibition of PDE5 by vardenafil enhances erectile function by increasing the amount of cyclic GMP.5

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Humans
URetinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
allosteric modulator
Humans
URetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
inhibitor
allosteric modulator
Humans
Absorption

Over the recommended dose range, vardenafil has a dose-proportional pharmacokinetics profile. In healthy male volunteers given a single oral dose of 20 mg of vardenafil, maximum plasma concentrations were reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state, and 0.00018% of the dose was detected in semen 1.5 hours after dosing. Vardenafil has a bioavailability of approximately 15%.5 High-fat meals cause a Cmax reduction of 18%-50%; however, no changes were detected in AUC or Tmax.5,6

Volume of distribution

Vardenafil has a steady-state volume of distribution of 208 L.5

Protein binding

Approximately 95% of vardenafil and its major circulating metabolite is bound to plasma proteins. Their protein binding is reversible and independent of total drug concentrations.5

Metabolism

Vardenafil is mainly metabolized by CYP3A4 in the liver, although CYP3A5 and CYP2C isoforms also contribute to its metabolism. The major circulating metabolite, M1 (N-desethylvardenafil), results from desethylation at the piperazine moiety of vardenafil, and has a plasma concentration of approximately 26% of that of the parent compound. M1 has a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil.5

Hover over products below to view reaction partners

Route of elimination

Vardenafil is excreted as metabolites mainly through feces and urine. Approximately 91-95% of administered oral dose is found in feces, while 2-6% of administered oral dose is found in urine.5

Half-life

Vardenafil and its primary metabolite (M1) have a terminal half-life of 4-5 hours.5

Clearance

Vardenafil has a total body clearance of 56 L/h.5

Adverse Effects
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Toxicity

Healthy male volunteers given a single dose of 120 mg of vardenafil experienced reversible back pain, myalgia and abnormal vision. Patients given vardenafil once daily over 4 weeks in single doses up to 80 mg and multiple doses up to 40 mg did not present serious adverse side effects. Cases of severe back pain were observed when 40 mg of vardenafil was administered twice daily; however patients did not present muscle or neurological toxicity. In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance as vardenafil is highly bound to plasma proteins and not significantly eliminated in the urine.5,6

No carcinogenic effects were detected in rats and mice given vardenafil daily for 24 months. Vardenafil was not mutagenic or clastogenic, and did not have an effect in fertility in male and female rats given up to 100 mg/kg/day for 28 days prior to mating in males, and for 14 days prior to mating and through day 7 of gestation in females.5,6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe risk or severity of hypotension can be increased when Vardenafil is combined with Abaloparatide.
AbametapirThe serum concentration of Vardenafil can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Vardenafil can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Vardenafil.
AbrocitinibThe serum concentration of Vardenafil can be increased when it is combined with Abrocitinib.
Food Interactions
  • Avoid grapefruit products. Vardenafil is metabolized by CYP3A4, and grapefruit products are CYP3A4 inhibitors; therefore, coadministration may increase serum levels of vardenafil and result in increased hypotension. .
  • Take with or without food. High-fat meals reduce the Cmax of vardenafil; however, there are no changes in AUC or Tmax.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Vardenafil hydrochloride5M8S2CU0TS330808-88-3FBCDRHDULQYRTB-UHFFFAOYSA-N
Product Images
International/Other Brands
Levitra (Bayer) / Staxyn (GlaxoSmithKline)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LevitraTablet, orally disintegrating10 mgOralBayer Ag2016-09-08Not applicableEU flag
LevitraTablet, film coated10 mg/1OralPd Rx Pharmaceuticals, Inc.2008-05-152016-12-15US flag
LevitraTablet, orally disintegrating10 mgOralBayer Ag2016-09-08Not applicableEU flag
LevitraTablet, film coated20 mg/1OralSchering Plough2008-05-152013-07-01US flag
LevitraTablet5 mgOralBayer2004-03-172020-11-16Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-vardenafilTablet20 mgOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-vardenafilTablet10 mgOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-vardenafilTablet5 mgOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-vardenafilTablet5 mgOralApotex Corporation2018-12-21Not applicableCanada flag
Apo-vardenafilTablet20 mgOralApotex Corporation2018-12-21Not applicableCanada flag

Categories

ATC Codes
G04BE09 — Vardenafil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Phenoxy compounds / Phenol ethers / N-alkylpiperazines / Alkyl aryl ethers / Organosulfonamides / N-substituted imidazoles / 1,2,4-triazines / Sulfonyls / Heteroaromatic compounds
show 5 more
Substituents
1,2,4-triazine / 1,4-diazinane / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenesulfonamide / Benzenesulfonyl group / Ether
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-alkylpiperazine, imidazotriazine, N-sulfonylpiperazine (CHEBI:46295)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
UCE6F4125H
CAS number
224785-90-4
InChI Key
SECKRCOLJRRGGV-UHFFFAOYSA-N
InChI
InChI=1S/C23H32N6O4S/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)
IUPAC Name
2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propyl-1H,4H-imidazo[4,3-f][1,2,4]triazin-4-one
SMILES
CCCC1=NC(C)=C2N1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(CC)CC1

References

Synthesis Reference

Yogesh S. Deshpande, Sandra Brueck, Julia Schulze Nahrup, Birgit Schnitter, Ganesh Gat, Javed Hussain, "PROCESS FOR THE PREPARATION OF A MEDICAMENT COMPRISING VARDENAFIL HYDROCHLORIDE TRIHYDRATE." U.S. Patent US20100159003, issued June 24, 2010.

US20100159003
General References
  1. Forstermann U, Sessa WC: Nitric oxide synthases: regulation and function. Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d. doi: 10.1093/eurheartj/ehr304. Epub 2011 Sep 1. [Article]
  2. Jing ZC, Yu ZX, Shen JY, Wu BX, Xu KF, Zhu XY, Pan L, Zhang ZL, Liu XQ, Zhang YS, Jiang X, Galie N: Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2011 Jun 15;183(12):1723-9. doi: 10.1164/rccm.201101-0093OC. Epub 2011 Mar 11. [Article]
  3. Authors unspecified: Vardenafil. . [Article]
  4. Rosen RC, Kostis JB: Overview of phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol. 2003 Nov 6;92(9A):9M-18M. doi: 10.1016/s0002-9149(03)00824-5. [Article]
  5. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  6. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
  7. Health Canada Approved Drug Products: STAXYN (vardenafil) orally disintegrating tablets (February 2020) [Link]
Human Metabolome Database
HMDB0015000
KEGG Drug
D08668
PubChem Compound
110634
PubChem Substance
46506777
ChemSpider
99300
BindingDB
14776
RxNav
306674
ChEBI
46295
ChEMBL
CHEMBL1520
ZINC
ZINC000018324776
Therapeutic Targets Database
DAP000414
PharmGKB
PA10229
PDBe Ligand
VDN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Vardenafil
PDB Entries
1uho / 1xot / 1xp0 / 3b2r / 7jsn

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS)1somestatusstop reasonjust information to hide
4CompletedTreatmentEndothelial Dysfunction / Erectile Dysfunction / Hypertension Arterial1somestatusstop reasonjust information to hide
4CompletedTreatmentErectile Dysfunction15somestatusstop reasonjust information to hide
4CompletedTreatmentErectile Dysfunction / Sexual Dysfunctions1somestatusstop reasonjust information to hide
4CompletedTreatmentErectile Dysfunction / Spinal Cord Injuries1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
  • A-S Medication Solutions LLC
  • Bayer Healthcare
  • Bryant Ranch Prepack
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Redpharm Drug
  • Schering Corp.
  • Va Cmop Dallas
Dosage Forms
FormRouteStrength
Tablet, film coatedOral20 MG
TabletOral20 mg
TabletOral5 mg
Tablet, coatedOral
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral5 mg/1
Tablet, solubleOral
Tablet, orally disintegratingOral10.0 mg
Tablet, film coatedOral11.852 mg
Tablet, film coatedOral23.705 mg
Tablet, film coatedOral5.926 mg
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral11.85 mg/1
TabletOral11.85 mg/1
Tablet, film coatedOral
Tablet, orally disintegratingOral10 MG
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Tablet, film coatedOral10 MG
Tablet, film coatedOral5 MG
Tablet, orally disintegratingOral
Tablet, coatedOral10 MG
TabletOral10 mg
Tablet, coatedOral20 mg
Tablet, coatedOral5 mg
Prices
Unit descriptionCostUnit
Levitra 10 mg tablet19.04USD tablet
Levitra 20 mg tablet19.04USD tablet
Levitra 5 mg tablet19.04USD tablet
Levitra 2.5 mg tablet18.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2309332No2002-12-032018-10-31Canada flag
US6362178No2002-03-262018-10-31US flag
US7696206No2010-04-132018-10-31US flag
US8273876No2012-09-252027-07-23US flag
US8841446No2014-09-232023-07-03US flag
US8613950No2013-12-242028-12-23US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)192 °CPatent US 9,845,328 B2
water solubility0.11 mg/mL (HCl salt)FDA label
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.325 mg/mLALOGPS
logP2.18ALOGPS
logP1.43Chemaxon
logS-3.2ALOGPS
pKa (Strongest Acidic)11.75Chemaxon
pKa (Strongest Basic)6.21Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area109.13 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity142.71 m3·mol-1Chemaxon
Polarizability53.22 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6682
Caco-2 permeable+0.5502
P-glycoprotein substrateSubstrate0.7415
P-glycoprotein inhibitor IInhibitor0.6976
P-glycoprotein inhibitor IIInhibitor0.8552
Renal organic cation transporterNon-inhibitor0.6975
CYP450 2C9 substrateNon-substrate0.6386
CYP450 2D6 substrateSubstrate0.7909
CYP450 3A4 substrateSubstrate0.697
CYP450 1A2 substrateNon-inhibitor0.8215
CYP450 2C9 inhibitorInhibitor0.7426
CYP450 2D6 inhibitorNon-inhibitor0.8464
CYP450 2C19 inhibitorNon-inhibitor0.7472
CYP450 3A4 inhibitorInhibitor0.8857
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7205
Ames testNon AMES toxic0.5748
CarcinogenicityNon-carcinogens0.6141
BiodegradationNot ready biodegradable0.8875
Rat acute toxicity2.6208 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8367
hERG inhibition (predictor II)Inhibitor0.7696
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-03di-9304600000-78a6e2bde8e38b367f38
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000i-0040900000-a78a646244f2fb1f6276
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000f-0011900000-88f62b9a8f7aec917a41
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0092000000-cf98ecae287c01370dbc
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0002900000-0b3a3d3b8a696b6c1c84
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-052r-0000900000-e57c1c9091e26873edc4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0001900000-9f332b16d2a563673357
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-0901600000-4231ac001d7a0b4e7bc1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-02mi-2501900000-2c2edea1cbb4c1a058e2
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0101900000-94265f5da0fe5589caf3
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-240.2311048
predicted
DarkChem Lite v0.1.0
[M-H]-213.71483
predicted
DeepCCS 1.0 (2019)
[M+H]+240.7878048
predicted
DarkChem Lite v0.1.0
[M+H]+216.1104
predicted
DeepCCS 1.0 (2019)
[M+Na]+239.8316048
predicted
DarkChem Lite v0.1.0
[M+Na]+222.02293
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da
References
  1. Blount MA, Zoraghi R, Ke H, Bessay EP, Corbin JD, Francis SH: A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization. Mol Pharmacol. 2006 Nov;70(5):1822-31. Epub 2006 Aug 22. [Article]
  2. Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6. [Article]
  3. Kim NN, Huang YH, Goldstein I, Bischoff E, Traish AM: Inhibition of cyclic GMP hydrolysis in human corpus cavernosum smooth muscle cells by vardenafil, a novel, selective phosphodiesterase type 5 inhibitor. Life Sci. 2001 Sep 28;69(19):2249-56. [Article]
  4. Saenz de Tejada I, Angulo J, Cuevas P, Fernandez A, Moncada I, Allona A, Lledo E, Korschen HG, Niewohner U, Haning H, Pages E, Bischoff E: The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res. 2001 Oct;13(5):282-90. [Article]
  5. Scheen AJ: [Medication of the month. Vardenafil (Levitra)]. Rev Med Liege. 2003 Sep;58(9):576-9. [Article]
  6. Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. [Article]
  7. Wang H, Ye M, Robinson H, Francis SH, Ke H: Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. [Article]
  8. Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [Article]
  9. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  10. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Allosteric modulator
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6G
Uniprot ID
P18545
Uniprot Name
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9643.09 Da
References
  1. Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [Article]
  2. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  3. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Allosteric modulator
General Function
Enzyme inhibitor activity
Specific Function
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Gene Name
PDE6H
Uniprot ID
Q13956
Uniprot Name
Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Molecular Weight
9074.36 Da
References
  1. Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [Article]
  2. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  3. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sheweita SA, Wally M, Hassan M: Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats. Oxid Med Cell Longev. 2016;2016:4970906. doi: 10.1155/2016/4970906. Epub 2016 Oct 9. [Article]
  2. Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [Article]
  3. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [Article]
  4. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  5. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Huang SA, Lie JD: Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul;38(7):407-19. [Article]
  2. Ku HY, Ahn HJ, Seo KA, Kim H, Oh M, Bae SK, Shin JG, Shon JH, Liu KH: The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90. doi: 10.1124/dmd.107.020099. Epub 2008 Feb 28. [Article]
  3. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  4. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  2. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  2. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  2. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  2. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ding PR, Tiwari AK, Ohnuma S, Lee JW, An X, Dai CL, Lu QS, Singh S, Yang DH, Talele TT, Ambudkar SV, Chen ZS: The phosphodiesterase-5 inhibitor vardenafil is a potent inhibitor of ABCB1/P-glycoprotein transporter. PLoS One. 2011 Apr 28;6(4):e19329. doi: 10.1371/journal.pone.0019329. [Article]
  2. Choi MK, Song IS: Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil. J Pharm Pharmacol. 2012 Aug;64(8):1074-83. doi: 10.1111/j.2042-7158.2012.01498.x. Epub 2012 Mar 16. [Article]
  3. Chen JJ, Sun YL, Tiwari AK, Xiao ZJ, Sodani K, Yang DH, Vispute SG, Jiang WQ, Chen SD, Chen ZS: PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter. Cancer Sci. 2012 Aug;103(8):1531-7. doi: 10.1111/j.1349-7006.2012.02328.x. Epub 2012 Jul 6. [Article]
  4. Tiwari AK, Chen ZS: Repurposing phosphodiesterase-5 inhibitors as chemoadjuvants. Front Pharmacol. 2013 Jun 25;4:82. doi: 10.3389/fphar.2013.00082. eCollection 2013. [Article]
  5. FDA Approved Drug Products: LEVITRA (vardenafil hydrochloride) tablets for oral use (March 2023) [Link]
  6. FDA Approved Drug Products: STAXYN (vardenafil hydrochloride) orally disintegrating tablets (March 2023) [Link]

Drug created at June 13, 2005 13:24 / Updated at July 22, 2024 19:44