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The Clinical Pharmacology and Pharmacokinetics of Cialis Cialis is an oral treatment for erectile dysfunction with an empirical formula of C22H19N3O4 representing a molecular weight of 389.41. This drug is available as a film coated, almond-shaped tablets for oral administration. The inactive ingredients of this drug are the following: microcrystalline cellulose, sodium lauryl sulfate, lactose monohydrate, magnesium stearate, talc, titanium dioxide, croscarmellose sodium, hydroxypropyl cellulose, iron oxide and triacetin.
The mechanism of action: Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. The response is mediated by the release of nitric oxide 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 and the inhibition of phosphodiesterase type 5 enhances erectile function by increasing the amount of cGMP. Cialis inhibits PDE5 because of sexual stimulation is required to initiate the local release of nitric oxide and the effect of this drug has no effect in the absence of sexual stimulation.
Studies in vitro have demonstrated that Cialis is a selective inhibitor of PDE5 and is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, platelets, skeletal muscle, kidney, cerebellum, lung and pancreas. In vitro studies have shown that the effect of Cialis is more potent on PDE5 than on other phosphodiesterases.
Cialisis >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, Cialis is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. This drug is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10 and 14-fold more potent for PDE5 than for PDE11A1, an enzyme found in human skeletal muscle. Cialis inhibits human recombinant PDE11A1 activity at concentrations within the therapeutic range.
Elimination: The mean oral clearance for Cialis is 2.5 L/ hr and the mean terminal half-life is 17.5 hours in healthy subjects. This drug 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).
Pharmacokinetics in Special Populations
Geriatric ?
Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) with no effect on Cmax relative to that observed in healthy subjects 19 to 45 years of age. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered (see Geriatric Use under PRECAUTIONS).
Pediatric ?
Tadalafil has not been evaluated in individuals less than 18 years old.
Hepatic Impairment ?
In clinical pharmacology studies, tadalafil exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C). Therefore, for patients with mild or moderate hepatic impairment, the maximum dose should not exceed 10 mg, and use in patients with severe hepatic impairment is not recommended (see DOSAGE AND ADMINISTRATION).
Renal Insufficiency ?
In clinical pharmacology studies using single-dose tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with mild (creatinine clearance 51 to 80 mL/ min) or moderate (creatinine clearance 31 to 50 mL/ min) renal insufficiency. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in Cmax and 2.7-to 4.1-fold increase in AUC following single-dose administration of 10 or 20 mg tadalafil.