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药品详细

Tadalafil(他达拉非)

化学结构式图
中文名
他达拉非
英文名
Tadalafil
分子式
C22H19N3O4
化学名
(2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0^{3,8}.0^{11,16}]heptadeca-1(10),11,13,15-tetraene-4,7-dione
分子量
Average: 389.404
Monoisotopic: 389.137556111
CAS号
171596-29-5
ATC分类
G04B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Tadalafil is an orally adminstered drug used to treat male erectile dysfunction (impotence). It is marketed worldwide under the brand name Cialis. 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. [Wikipedia]

生产厂家
  • Eli lilly and co
  • Eli Lilly and Company
  • Eli lilly co
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. Pubmed
  2. Burnett AL: Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health. J Androl. 2007 Oct 17;. Pubmed
  3. Guazzi M, Samaja M: The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem. 2007;14(20):2181-91. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Tryptamines and Derivatives
  • Lactams
Substructures
  • Acetals and Derivatives
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Pyrroles
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Tryptamines and Derivatives
  • Dioxoles
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzodioxoles
  • Anisoles
  • Carboxamides and Derivatives
  • Lactams
  • Imines
  • Phenyl Esters
适应症
药理
Indication Used for the treatment of erectile dysfunction.
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 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.
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%
Metabolism
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.
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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 301-302 °C Not Available
water solubility Practically insoluble in water Not Available
logP 1.7 Not Available
Predicted Properties
Property Value Source
water solubility 2.50e-01 g/l ALOGPS
logP 2.36 ALOGPS
logP 1.64 ChemAxon
logS -3.2 ALOGPS
pKa (strongest acidic) 15.17 ChemAxon
pKa (strongest basic) -4.2 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 74.87 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 104.08 ChemAxon
polarizability 40.92 ChemAxon
药物相互作用
Drug Interaction
Alfuzosin Tadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
Amprenavir Amprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Atazanavir Atazanavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Azilsartan medoxomil Pharmacodynamic synergist- increases effects.
Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Clarithromycin Clarithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Conivaptan Conivaptan may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Darunavir Darunavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Delavirdine Delavirdine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Doxazosin Tadalafil may enhance the hypotensive effect of Doxazosin. Monitor for hypotension during concomitant therapy.
Fosamprenavir Fosamprenavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Imatinib Imatinib may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Indinavir Indinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isoniazid Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Isosorbide Dinitrate The vasodilatory effects of Isosorbide dinitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Isosorbide Mononitrate The vasodilatory effects of Isosobide mononitrate may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Itraconazole Itraconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Ketoconazole Ketoconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Lopinavir Lopinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Miconazole Miconazole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nefazodone Nefazodone may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nelfinavir Nelfinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nicardipine Nicardipine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Nitroglycerin The vasodilatory effects of Nitroglycerin may be increased by Tadalafil. Severe hypotension may occur. Concomitant therapy is contraindicated.
Pentaerythritol Tetranitrate Possible significant hypotension with this combination
Phenoxybenzamine Tadalafil may enhance the hypotensive effect of Phenoxybenzamine. Monitor for hypotension during concomitant therapy.
Phentolamine Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Posaconazole Posaconzole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Prazosin Tadalafil may enhance the hypotensive effect of Prazosin. Monitor for hypotension during concomitant therapy.
Quinidine Quinidine may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Rifampin Rifampin may reduce Tadalafil plasma concentrations and efficacy.
Ritonavir Ritonavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Saquinavir Saquinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Tamsulosin Tadalafil may enhance the hypotensive effect of Tamsulosin. Monitor for hypotension during concomitant therapy.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin Telithromycin may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Terazosin Tadalafil may enhance the hypotensive effect of Terazosin. Monitor for hypotension during concomitant therapy.
Tipranavir Tipranavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tadalafil by decreasing its metabolism. Concomitant therapy should be avoided if possible due to high risk of tadalafil toxicity.
食物相互作用
Not Available

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