Introduction
Tadalafil is an orally administered drug used to treat male erectile dysfunction (impotence). 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.
Uses
Tadalafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension.
Used for the treatment of erectile dysfunction.
Associated Conditions
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
Penile erection during sexual stimulation is achieved by the relaxation of penile arteries and corpus cavernosal smooth muscles, leading to increased blood flow to the organ. 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, and is degraded by the cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum located around the penis. Tadalafil inhibits PDE5 and thereby enhances erectile function by increasing the amount of cGMP available.
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
- 63 L
Protein Binding
94%
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.
Food Interactions
- Avoid excessive or chronic alcohol consumption. Ingesting excess amounts of alcohol (more than four drinks in a short time) may potentiate the hypotension and dizziness caused by tadalafil.
- Avoid grapefruit products. Tadalafil is metabolized by CYP3A4, and grapefruit products are CYP3A4 inhibitors; therefore, coadministration may increase serum levels of tadalafil and result in increased hypotension.
- Take with or without food.
Dosage
Erectile Dysfunction: For most patients the recommended starting dose is 10 mg. The dose may be increased to 20 mg or decreased to 5 mg based on requirement. The maximum dosing frequency is once daily. Tadalafil is effective for up to 36 hours.
Benign prostatic hyperplasia: The recommended dose is 5 mg taken at the same time every day.
Combined Erectile Dysfunction and Benign prostatic hyperplasia: The recommended dose is 5 mg at the same time every day.
