| Indication |
Used for the treatment of erectile dysfunction. |
| Pharmacodynamics |
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. |
| 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. |
| 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. |
| Volume of distribution |
|
| Protein binding |
94% |
| Metabolism |
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 |
|
| Toxicity |
Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity. |
