Talafil Mechanism of Action

Pharmacology: Pharmacodynamics: Tadalafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide in the corpus cavernosum, nitric oxide activates the enzyme guanylate cyclase, which stimulates the synthesis of cyclic guanosine monophosphate (cGMP). cGMP produces smooth muscle relaxation and increased blood flow into the corpora cavernosa, thereby producing an erection. Tadalafil has no effect in the absence of sexual stimulation.
Tadalafil is > 10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4 and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leucocytes, skeletal muscle, and other organs. Tadalafil is > 10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Tadalafil is >700-fold more potent for PDE5 than for PDE6, which is found in the retina and phototransduction. Tadalafil is > 9,000-fold more potent for PDE5 than PDE8, PDE9, PDE10 and 14-fold more potent for PDE5 than PDE11.
5 mg Tablet: The effect of PDE5 inhibitors on cGMP concentration in the corpus cavernosum is also observed in the smooth muscle of prostate and bladder. The resulting vascular relaxation increase blood perfusion.
Pharmacokinetics: Absorption: Tadalafil is readily absorbed after oral administration and the mean maximum observed plasma concentration (Cmax) is achieved at a median time of 2 hours after dosing. Absolute bioavailability of tadalafil following oral dosing has not been determined. The rate and extent of absorption of tadalafil are not influenced by food.
Distribution: The mean volume of distribution is approximately 63 liters. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.
Metabolism: Tadalafil is predominantly metabolised by the cytochrome P450 (CYP) 3A4 isoform. The major circulating metabolite is the methylcatechol glucuronide. It is not expected to be clinically active at observed metabolite concentrations.
Elimination: The mean oral clearance for tadalafil is 2.5 L/h and the mean half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).