Overview
| Generic Names: | CIA; ICOS 351; Tadanafil; tadalafil |
|---|---|
| IUPAC Name: | (6R-trans)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione |
| Trade Names: | Cialis; Cialis/Tadalafil Hcl; Cialis/Taladafil |
| PharmGKB Accession Id: | PA10333 |
Description
Tadalafil is an orally adminstered drug used to treat male erectile dysfunction (impotence). It is marketed worldwide under the brand name Cialis. It is a phosphodiesterase 5 (PDE5) inhibitor. Tadalafil's distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours). This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the "weekend pill." This longer half-life also is the basis of current investigation for tadalafil's use in pulmonary arterial hypertension as a once-daily therapy. [Wikipedia]
Indication
Used for the treatment of erectile dysfunction
ATC Therapeutic Category
- G04BE:Drugs used in erectile dysfunction
Pharmacology and Interactions
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 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.
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), 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.
Absorption, Distribution, Metabolism, Elimination & Toxicity
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.
Protein Binding
94%
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.
Half Life
17.5 hours
Toxicity
Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity.
Chemical Properties
Chemical Formula:
C22H19N3O4
SMILES Code:
CN1CC(=O)N2[C@@H](C1=O)CC3=C([C@H]2C4=CC5=C(C=C4)OCO5)NC6=CC=CC=C36
(Format: OpenEye Isomeric)
Molecular Weight ( average / monoisotopic )
389.404 / 389.1376
Curated Information
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
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CYP3A |
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CYP3A4 |
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CYP3A5 |
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ENPP5 |
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Non-Curated Information
A list of non-curated publications that mention this drug along with other genes is available.
Metabolizing Enzymes
Drug Targets
Non-Curated Information
A list of non-curated publications that mention this drug along with other drugs is available.
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
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Raynaud Disease |
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Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
LinkOuts
Common Searches
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Non-Curated Publications
A list of non-curated publications that mention this drug is available.