QuickView for Vardenafil (compound)

Summary
General Info

PubChem

PubChem Compound 110634

Name:	vardenafil
PubChem Compound ID:	110634
Molecular formula:	C₂₃H₃₂N₆O₄S
Molecular weight:	488.604 g/mol
Synonyms:	VDN; HSDB 7304; Levitra; VARDENAFIL, LEVITRA; 224785-90-4; 2-(2-Ethoxy-5-(4-ethylpiperazin-1-yl-1-sulfonyl)phenyl)-5-methyl-7-propyl-3H-imidazo(5,1-f)(1,2,4)triazin-4-one; 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-; Vardenafil; 2-{2-ETHOXY-5-[(4-ETHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-5-METHYL-7-PROPYLIMIDAZO[5,1-F][1,2,4]TRIAZIN-4(1H)-ONE

DrugBank

Identification

Name:	vardenafil
Name (isomeric):	DB00862
Drug Type:	small molecule
Synonyms:	VDN
Brand:	Levitra
Category:	Phosphodiesterase Inhibitors, Vasoconstrictor Agents, Anti-Impotence Agents
CAS number:	224785-90-4

Pharmacology

Indication:	Used for the treatment of erectile dysfunction
Pharmacology:	Vardenafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), le... show more » Vardenafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Vardenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with vardenafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, vardenafil should not cause an erection. show less «
Mechanism of Action:	Vardenafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP 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 i... show more » Vardenafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP 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 cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by vardenafil enhances erectile function by increasing the amount of cGMP. show less «
Absorption:	Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%.
Protein binding:	95%
Biotransformation:	Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. M1 shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil.
Route of elimination:	After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).
Half Life:	4-5 hours
Clearance:	56 L/h
Toxicity:	Symptoms of overdose include vision changes and back and muscle pain.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Atazanavir	Atazanavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Ketoconazole	Ketoconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Isosorbide Mononitrate	The vasodilatory effects of Isosorbide mononitrate may be increased by Vardenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Indinavir	Indinavir, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Delavirdine	Delavirdine, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.

Atazanavir	Atazanavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Ketoconazole	Ketoconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Isosorbide Mononitrate	The vasodilatory effects of Isosorbide mononitrate may be increased by Vardenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Indinavir	Indinavir, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Delavirdine	Delavirdine, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Nefazodone	Nefazodone, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Terazosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Terazosin, may occur. Monitor for hypotension during concomitant therapy.
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Vardenafil. Concomitant therapy is contraindicated.
Erythromycin	Erythromycin, a moderate CYP3A4 inhibitor, may reduce the metabolism and clearance of vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of vardenafil if erythromycin is initiated, discontinued or dose changed.
Posaconazole	Posaconazole, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Lopinavir	Lopinavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Telithromycin	Telithromycin, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Silodosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Silodosin, may occur. Monitor for hypotension during concomitant therapy.
Phentolamine	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phentolamine, may occur. Monitor for hypotension during concomitant therapy.
Saquinavir	Saquinavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Darunavir	Darunavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Doxazosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Doxazosin, may occur. Monitor for hypotension during concomitant therapy.
Conivaptan	Conivaptan, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Tamsulosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Tamsulosin, may occur. Monitor for hypotension during concomitant therapy.
Alfuzosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Alfuzosin, may occur. Monitor for hypotension during concomitant therapy.
Itraconazole	Itraconazole, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.
Isosorbide Dinitrate	The vasodilatory effects of Isosorbide dinitrate may be increased by Vardenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Amprenavir	Amprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Fosamprenavir	Fosamprenavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Procainamide	Increased risk of cardiotoxicity and arrhythmias
Phenoxybenzamine	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phenoxybenzamine, may occur. Monitor for hypotension during concomitant therapy.
Nitroglycerin	The vasodilatory effects of Nitroglycerin may be increased by Vardenafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Isoniazid	Isoniazid, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Pentaerythritol Tetranitrate	Possible significant hypotension with this combination
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of vardenafil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of vardenafil if voriconazole is initiated, discontinued or dose changed.
Prazosin	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Prazosin, may occur. Monitor for hypotension during concomitant therapy.
Amiodarone	Increased risk of cardiotoxicity and arrhythmias
Imatinib	Imatinib, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Clarithromycin	Clarithromycin, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Miconazole	Miconazole, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Quinidine	Quinidine, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Nicardipine	Nicardipine, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Nelfinavir	Nelfinavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
Ritonavir	Ritonavir, a potent CYP3A4 inhibitor, may decrease the metabolism and clearance of Vardenafil. Concomitant therapy is contraindicated.

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Targets

cGMP-specific 3',5'-cyclic phosphodiesterase

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

UniProt ID:

O76074

Gene:

PDE5A

Actions:

inhibitor

References:

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.
View Article

Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6.
View Article

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

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.
View Article

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.
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Scheen AJ: [Medication of the month. Vardenafil (Levitra)] Rev Med Liege. 2003 Sep;58(9):576-9.
View Article

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.
View Article

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.
View Article

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.
View Article

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

Enzymes

Cytochrome P450 3A4

Cytochrome P450 3A5