Тадалафил

Описание

Tadalafil (market name “Cialis” or “Adcirca”) was developed by American pharmaceutical company Lilly. It is a kind of PDE5 inhibitor used for the treatment of erectile dysfunction, benign prostatic hypertrophy and pulmonary arterial hypertension.The effect of Tadalafil is relaxing the blood vessels muscles and increasing the blood flow into the corpus cavernosum. Studies show that Cialis works very quickly, taking effect in around 15-20 minutes, and has a prolonged effect that can last for up to 36 hours. T1/2 is 17.5h.

Химические свойства

White to Off-White Cyrstalline Solid

Определение

ChEBI: Tadalafil is a pyrazinopyridoindole that is 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione substituted at position 2 by a methyl group and at position 6 by a 1,3-benzodioxol-5-yl group (the 6R,12aR-diastereomer). A phosphodiesterase V inhibitor inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension. It has a role as an EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor and a vasodilator agent. It is a pyrazinopyridoindole and a member of benzodioxoles.

Общее описание

Tadalafil, 171596-29-5, is a potent PDE5 inhibitor.It received FDA approval for the treatment of erectiledysfunction in December 2003. Because of its half-life of17.5 hours, it is marketed as a 36-hour treatment. Tadalafil ispredominantly metabolized by hepatic enzymes, includingCYP3A4. The concomitant use of CYP3A4 inhibitors suchas ritonavir, indinavir, ketoconazole, as well as moderateCYP3A inhibitors such as erythromycin have been shown toresult in significant increases in tadalafil plasma levels.Much like sildenafil, tadalafil is under clinical investigationfor managing PAH.

Механизм действия

The mechanism of action of tadalafil is through inhibiting the activity of the cGMP specific phosphodiesterase type 5 (PDE5). PDE5 degrades cGMP in the corpus cavernosum located around the penis. Therefore, tadalafi leads to the increased concentration of cGMP which further causes the smooth muscle relaxation and increased blood flow into the corpus cavernosum. Some clinical studies also implied that tadalafil could improve endothelia function in men with increased cardiovascular risk and lower the urinary tract symptoms secondary to benign prostatic hyperplasia.

Фармакокине?тика

Tadalafil is different in structure from both sildenafil and vardenafil. It is rapidly absorbed and peaks in concentration (378 μg/L after a 20-mg dose) after 2 hours, displaying a long half-life of 17.5 hours. It also is metabolized by the liver (CYP3A4). Notably, its pharmacokinetics is not clinically influenced by alcohol or food intake or by factors such as diabetes or impaired hepatic or renal function.

Побочные эффекты

The most common drug-related adverse events are headache, back pain, dyspepsia, and myalgia. At 10 and 20 mg doses, Tadalafil does not have a significant effect on blood pressure and heart rate and does not result in increased instances of myocardial infarction. Rare reports of prolonged erections greater than 4 h and priapism have been noted with the use of tadalafil. Priapism, if not treated properly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 h are advised to seek emergency medical attention.

Метаболизм

Tadalafil(171596-29-5) is metabolised in the liver mainly by the cytochrome P450 isoenzyme CYP3A4. The major metabolite, the methylcatechol glucuronide, is inactive. Tadalafil is excreted, mainly as metabolites, in the faeces (61% of the dose), and to a lesser extent the urine (36% of the dose).

использованная литература

https://www.drugs.com/tadalafil.html
https://www.drugbank.ca/drugs/DB00820
Roehrborn, C. G., et al. "Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study." Journal of Urology 180.4(2008):1228.
Rosano, Giuseppe M. C., et al. "Chronic Treatment with Tadalafil Improves Endothelial Function in Men with Increased Cardiovascular Risk." European Urology 47.2(2005):214-222.