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Tadalafil
drug data and news
Tadalafil drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Tadalafil | ||
| Brand Names/Synonyms | CIA; Cialis; Cialis/Tadalafil Hcl; Cialis/Taladafil; IC 351; ICOS 351; Tadalafil; Tadanafil | ||
| Indication | Used for the treatment of erectile dysfunction | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | 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 | Tadalafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. 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. The inhibition of phosphodiesterase type 5 (PDE5) by Tadalafil enhances erectile function by increasing the amount of cGMP. | ||
| Tadalafil News (When available) |
Chinese Herbal Medicines 16 May 2006 Cialis – The Le weekend drug May 13, 2006 Cialis - from impotence to competence May 11, 2006 A fairy tale of a drug May 13, 2006 COMUNICADO: Lilly ICOS LLC Reports Results for First Quarter of ... Apr 20, 2006 Enrich Life with Erectile Dysfunction Drug's Viagra and Cialis May 11, 2006 Treat Erectile Dysfunction May 9, 2006 Cialis - star performer solving erectile dysfunction May 8, 2006 AbelsonTaylor Announces Four New Appointments May 11, 2006 Threshold BPH Drug Hits Bump; Stock Tumbles On Liver Toxicity May 12, 2006 Cialis Is Effective In The Treatment Of Men With Erectile ... Apr 24, 2006 ICOS Corporation Reports Results for 2006 First Quarter; Strong ... May 4, 2006 Generic drug vs Erectile dysfunction problem May 1, 2006 Optic Neuropathy Patients Should Avoid Erectile Dysfunction Drugs May 1, 2006 Lilly Reports Q1 EPS of $.77, or 13% Growth Apr 20, 2006 Enhance your sexuality with cialis Apr 17, 2006 APS: Lilly ICOS LLC Reports Results for First Quarter of 2006 Apr 20, 2006 Long Term Use Of Oral PDE-5 Inhibitors May Treat And Prevent ... Apr 18, 2006 ICOS to Release Financial Results for 2006 First Quarter on May 4 ... Apr 24, 2006 | ||
| Dosage Forms | TABLET | ||
| Drug_Category | Vasoconstrictor Agents; Phosphodiesterase Inhibitors; ATC:G04BE08 | ||
| 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. | ||
| Interactions | Interactions for Tadalafil: Effects of Other Drugs on Tadalafil Cytochrome P450 Inhibitors: Tadalafil is a substrate of and predominantly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase tadalafil exposure. Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312% and Cmax by 22%, relative to the values for tadalafil 20 mg alone. Ketoconazole (200 mg daily) increased tadalafil 10-mg single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone. HIV Protease inhibitor: Ritonavir (200 mg twice daily), an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20-mg single-dose exposure (AUC) by 124% with no change in Cmax, relative to the values for tadalafil 20 mg alone. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure. Based upon these results, in patients taking concomitant potent CYP3A4 inhibitors, the dose of Tadalafil should not exceed 10 mg, and Tadalafil should not be taken more frequently than once in every 72 hours. Other cytochrome P450 inhibitors: Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. Cytochrome P450 Inducers: Studies have shown that drugs that induce CYP3A4 can decrease tadalafil exposure. Rifampin: Rifampin (600 mg daily), a CYP3A4 inducer, reduced tadalafil 10-mg single-dose exposure (AUC) by 88% and Cmax by 46%, relative to the values for tadalafil 10 mg alone. Although specific interactions have not been studied, other CYP3A4 inducers, such as carbamazepine, phenytoin, and phenobarbitol, would likely decrease tadalafil exposure. No dose adjustment is warranted. Gastrointestinal Drugs: H2 antagonists: An increase in gastric pH resulting from administration of nizatidine had no significant effect on tadalafil pharmacokinetics. Antacids: Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil. Effects of Tadalafil on Other Drugs: Drugs Metabolized by Cytochrome P450 Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms. Studies have shown that tadalafil does not inhibit or induce P450 isoforms CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. CYP1A2 substrate: Tadalafil had no clinically significant effect on the pharmacokinetics of theophylline. When tadalafil was administered to subjects taking theophylline, a small augmentation (3 beats per minute) of the increase in heart rate associated with theophylline was observed. CYP3A4 substrates: Tadalafil had no clinically significant effect on exposure (AUC) to midazolam or lovastatin. CYP2C9 substrate: Tadalafil had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin, nor did tadalafil affect changes in prothrombin time induced by warfarin. Alcohol Alcohol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. The interaction of tadalafil with alcohol was evaluated in 3 clinical pharmacology studies. In 2 of these, alcohol was administered at a dose of 0.7 g/kg, which is equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male, and tadalafil was administered at a dose of 10 mg in 1 study and 20 mg in another. In both these studies, all patients imbibed the entire alcohol dose within 10 minutes of starting. In one of these two studies, blood alcohol levels of 0.08% were confirmed. In these two studies, more patients had clinically significant decreases in blood pressure on the combination of tadalafil and alcohol as compared to alcohol alone. Some subjects reported postural dizziness, and orthostatic hypotension was observed in some subjects. When tadalafil 20 mg was administered with a lower dose of alcohol (0.6 g/kg, which is equivalent to approximately 4 ounces of 80-proof vodka, administered in less than 10 minutes), orthostatic hypotension was not observed, dizziness occurred with similar frequency to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Tadalafil did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations. Both alcohol and Tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with Tadalafil can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Anti-Hypertensives PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood-pressure-lowering effects of selected anti-hypertensive medications. Alpha Blockers Doxazosin: When tadalafil 20 mg was administered to healthy subjects taking doxazosin (8 mg daily), an alpha[1]-adrenergic blocker, there was significant augmentation of the blood-pressure-lowering effect of doxazosin. Tamsulosin: In a clinical pharmacology study, when a single dose of tadalafil 20 mg was administered to healthy subjects taking 0.4 mg once-daily tamsulosin, a selective alpha[1A]-adrenergic blocker, no significant decreases in blood pressure were observed. Therefore, based upon significant augmentation of the blood-pressure-lowering effect of doxazosin, an alpha[1]-adrenergic blocker, and no significant effect seen with 0.4 mg once-daily tamsulosin, a selective alpha[1A]-adrenergic blocker, administration of Tadalafil to patients taking any alpha-adrenergic blocker other than 0.4 mg once-daily tamsulosin is contraindicated. Other Anti-Hypertensive Agents Amlodipine: A study was conducted to assess the interaction of amlodipine (5 mg daily) and tadalafil 10 mg. There was no effect of tadalafil on amlodipine blood levels and no effect of amlodipine on tadalafil blood levels. The mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking amlodipine was 3/2 mm Hg, compared to placebo. In a similar study using tadalafil 20 mg, there were no clinically significant differences between tadalafil and placebo in subjects taking amlodipine. Metoprolol: A study was conducted to assess the interaction of sustained-release metoprolol (25 to 200 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking metoprolol was 5/3 mm Hg, compared to placebo. Bendrofluazide: A study was conducted to assess the interaction of bendrofluazide (2.5 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking bendrofluazide was 6/4 mm Hg, compared to placebo. Enalapril: A study was conducted to assess the interaction of enalapril (10 to 20 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking enalapril was 4/1 mm Hg, compared to placebo. Angiotensin II receptor blocker (and other anti-hypertensives): A study was conducted to assess the interaction of angiotensin II receptor blockers and tadalafil 20 mg. Subjects in the study were taking any marketed angiotensin II receptor blocker, either alone, as a component of a combination product, or as part of a multiple anti-hypertensive regimen. Following dosing, ambulatory measurements of blood pressure revealed differences between tadalafil and placebo of 8/4 mm Hg in systolic/diastolic blood pressure. Aspirin Tadalafil did not potentiate the increase in bleeding time caused by aspirin. | ||
| Toxicity | Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity. | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | (6R-trans)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione | ||
| Chemical Formula | C22H19N3O4 | ||
| Molecular Weight | 389.404 g/mol | ||
| Smiles String | CN1CC(=O)N2C(C1=O)CC3=C(C2C4=CC5=C(C=C4)OCO5)NC6=CC=CC=C36 | ||
| Melting Point | 301-302 °C | ||
| Water Solubility | Practically insoluble in water | ||
| State | Solid | ||
| LogP/Hphobicity | 1.35 | ||
| Isoelectric Point | Not Available | ||
| Biotransformation | Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. In vitro data suggests the metabolites are not expected to be pharmacologically active at observed metabolite concentrations. | ||
| Half Life | 17.5 hours | ||
| Protein Binding [%] | 94% | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.drugs.com/cons/Tadalafil.html http://www.rxlist.com/cgi/generic3/cialis.htm | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00071 | ||
| CAS Registry Number | 171596-29-5 | ||
| KEGG Compound ID | C13509 | ||
| PubChem ID | SID:687903 | ||
| PharmGKB ID | Not Available | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | 2248088 |
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