QuickView for Tadalafil (compound)

Summary
General Info

PubChem

PubChem Compound 110635

Name:	tadalafil
PubChem Compound ID:	110635
Molecular formula:	C₂₂H₁₉N₃O₄
Molecular weight:	389.404 g/mol
Synonyms:	Pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R-trans)-; Tadalafil (JAN/USAN); Cialis (TN); GF 196960; 171596-29-5; ICOS 351; IC-351; GF-196960; Cialis; Tadalafil. show more » Pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R-trans)-; Tadalafil (JAN/USAN); Cialis (TN); GF 196960; 171596-29-5; ICOS 351; IC-351; GF-196960; Cialis; Tadalafil; HSDB 7303; IC351; D02008; Pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-; IC 351; (6R,12aR)-2,3,6,7,12,12a-Hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dione; CIA show less «

DrugBank

Identification

Name:	tadalafil
Name (isomeric):	DB00820
Drug Type:	small molecule
Synonyms:	ICOS 351; CIA; Tadanafil
Brand:	Cialis
Category:	Vasodilator Agents, Phosphodiesterase Inhibitors
CAS number:	171596-29-5

Pharmacology

Indication:	Used for the treatment of erectile dysfunction.
Pharmacology:	Tadalafil 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), lea... show more » Tadalafil 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. Tadalafil 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 tadalafil 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, tadalafil should not cause an erection. show less «
Mechanism of Action:	Tadalafil 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... show more » Tadalafil 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 tadalafil enhances erectile function by increasing the amount of cGMP. show less «
Absorption:	After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.
Protein binding:	94%
Biotransformation:	Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. In vitro data suggests the metabolites are not expected to be pharmacologically active at observed metabolite concentrations.
Route of elimination:	Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Half Life:	17.5 hours
Clearance:	oral cl=2.5 L/hr
Toxicity:	Oral, Rat LD₅₀ = 2000 mg/kg, no deaths or toxicity.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Delavirdine	Delavirdine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Saquinavir	Saquinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isoniazid	Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Alfuzosin	Tadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
Ketoconazole	Ketoconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Delavirdine	Delavirdine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Saquinavir	Saquinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isoniazid	Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Alfuzosin	Tadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
Ketoconazole	Ketoconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Ritonavir	Ritonavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Telithromycin	Telithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Fosamprenavir	Fosamprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Doxazosin	Tadalafil may enhance the hypotensive effect of Doxazosin. Monitor for hypotension during concomitant therapy.
Rifampin	Rifampin may reduce Tadalafil plasma concentrations and efficacy.
Miconazole	Miconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Conivaptan	Conivaptan may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Phenoxybenzamine	Tadalafil may enhance the hypotensive effect of Phenoxybenzamine. Monitor for hypotension during concomitant therapy.
Tipranavir	Tipranavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Lopinavir	Lopinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Imatinib	Imatinib may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Amprenavir	Amprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Posaconazole	Posaconzole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Indinavir	Indinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Prazosin	Tadalafil may enhance the hypotensive effect of Prazosin. Monitor for hypotension during concomitant therapy.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tadalafil by decreasing its metabolism. Concomitant therapy should be avoided if possible due to high risk of tadalafil toxicity.
Isosorbide Dinitrate	The vasodilatory effects of Isosorbide dinitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Nitroglycerin	The vasodilatory effects of Nitroglycerin may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Pentaerythritol Tetranitrate	Possible significant hypotension with this combination
Phentolamine	Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Clarithromycin	Clarithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Itraconazole	Itraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Quinidine	Quinidine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Darunavir	Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Terazosin	Tadalafil may enhance the hypotensive effect of Terazosin. Monitor for hypotension during concomitant therapy.
Nelfinavir	Nelfinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isosorbide Mononitrate	The vasodilatory effects of Isosobide mononitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Nefazodone	Nefazodone may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nicardipine	Nicardipine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamsulosin	Tadalafil may enhance the hypotensive effect of Tamsulosin. Monitor for hypotension during concomitant therapy.
Atazanavir	Atazanavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

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Targets

cGMP-specific 3',5'-cyclic phosphodiesterase

Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A

Enzymes

Cytochrome P450 3A4