Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. It is taken by mouth. Onset is typically within half an hour and the duration is up to 36 hours.
Common side effects include headache, muscle pain, flushed skin, and nausea. Caution is advised in those with cardiovascular disease. Rare but serious side effects include a prolonged erection that can lead to damage to the penis, vision problems, and hearing loss. Tadalafil is not recommended in people taking nitrovasodilators such as nitroglycerin, as this may result in a serious drop in blood pressure. Tadalafil is a PDE5 inhibitor which increases blood flow to the penis. It also dilates blood vessels in the lungs, which lowers the pulmonary artery pressure.
Tadalafil was approved for medical use in the United States in 2003. It is available as a generic medication. In 2021, it was the 171st most commonly prescribed medication in the United States, with more than 3 million prescriptions.
Description
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.Tadalafil powder.
Chemical Properties White to Off-White Cyrstalline Solid
Uses Tadalafil is used for the treatment of erectile dysfunction. A phosphodiesterase 5 inhibitor.Tadalafil for sale
Definition 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.
Preparation Tadalafil is synthesized in three steps starting from D-tryptophan methyl ester, by first condensing with piperonal in a Pictet-Spengler cyclization reaction to form the tetrahydro-β-carboline derivative, which is followed by chloroacetylation of the piperidine ring nitrogen and cyclization with methylamine.
General Description
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.
Mechanism of action 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.
Pharmacokinetics 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.
Clinical Use
Tadalafil is one of the two new PDE5 inhibitors launched for the oral treatment of male erectile dysfunction. Tadalafil is a b-carboline derivative and it is structurally distinct from vardenafil (Levitraw) and sildenafil (Viagraw), both of which are PDE5 inhibitors based on a fused pyrimidine core structure.
Side effects 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.
Drug interactions
Potentially hazardous interactions with other drugs
Alpha-blockers: enhanced hypotensive effect – avoid concomitant use.
Antibacterials: concentration possibly increased by clarithromycin and erythromycin; concentration reduced by rifampicin – avoid.
Antifungals: concentration increased by ketoconazole – avoid; concentration possibly increased by itraconazole.
Antivirals: concentration possibly increased by fosamprenavir and indinavir; increased by ritonavir – avoid; increased risk of ventricular arrhythmias with saquinavir – avoid; avoid high doses of tadalafil with telaprevir.
Cobicistat: concentration of tadalafil possibly increased – reduce dose of tadalafil.
Nicorandil: possibly enhanced hypotensive effect – avoid concomitant use.
Nitrates: enhanced hypotensive effect – avoid concomitant use.
Riociguat: enhanced hypotensive effect – avoid concomitant use.
Metabolism
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).
storage Store at -20°C
Clinical claims and research In a study of 348 cases of mild to severe erectile dysfunction, patients were randomly given 20mg of Cialis or a placebo. Results showed that in comparison to the placebo group, patients who took Cialis experienced improved intercourse success in the 24-36 hours following medication, with many patients achieving successful sexual intercourse twice in 36 hours. Side effect rate and severity were also no different from those of the placebo group. Over 5% of patients in the Cialis group experienced headaches and indigestion.
Melting point 298-300°C
alpha D20 +71.0°
Boiling point 679.1±55.0 °C(Predicted)
density 1.51±0.1 g/cm3(Predicted)
Fp 2℃
storage temp. Sealed in dry,2-8°C
solubility DMSO: soluble20mg/mL, clear
form powder
pka 16.68±0.40(Predicted)
color white to beige
optical activity [α]/D +68 to +78°, c = 1 in chloroform-d
BCS Class 4
Stability: Unstable in Methanol
Bioavailability Varies
Protein binding 94%
Metabolism Liver (predominantly CYP3A4)
Metabolites Catechol metabolite
Onset of action 30 minutes
Elimination half-life 17.5 hours
Excretion Feces (~61%), urine (~36%)[5]
More Introduction:https://en.wikipedia.org/wiki/Tadalafil
