Tìm theo
Sildenafil
Các tên gọi khác (1) :
  • 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-D)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine
Hormon, Nội tiết tố
Thuốc Gốc
Small Molecule
CAS: 139755-83-2
ATC: G04BE03
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C22H30N6O4S
PTK: 474.576
Sildenfail is a vasoactive agent used to treat erectile dysfunction and reduce symptoms in patients with pulmonary arterial hypertension (PAH). Sildenafil elevates levels of the second messenger, cGMP, by inhibiting its breakdown via phosphodiesterase type 5 (PDE5). PDE5 is found in particularly high concentrations in the corpus cavernosum, erectile tissue of the penis. It is also found in the retina and vascular endothelium. Increased cGMP results in vasodilation which facilitates generation and maintenance of an erection. The vasodilatory effects of sildenafil also help reduce symptoms of PAH.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H30N6O4S
Phân tử khối
474.576
Monoisotopic mass
474.204924168
InChI
InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)
InChI Key
InChIKey=BNRNXUUZRGQAQC-UHFFFAOYSA-N
IUPAC Name
5-[2-ethoxy-5-(4-methylpiperazine-1-sulfonyl)phenyl]-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one
Traditional IUPAC Name
sildenafil
SMILES
CCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC1
Độ tan chảy
189-190 °C
Độ hòa tan
3.5 mg/mL
logP
1.9
logS
-3
pKa (strongest acidic)
7.27
pKa (Strongest Basic)
5.97
PSA
109.13 Å2
Refractivity
139.44 m3·mol-1
Polarizability
51.18 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
8
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Vasodilation results in high levels of blood flow causing the penis to grow to its full size. This stage is called tumescence. During the full-erection stage, blood flow fills penis sinusoids and outflow is restricted. This is followed by the rigid-erection phase during which the cavernous muscles contract causing the penis to become rigid. Little blood flow occurs during this stage. During the final stage, detumescence, the cavernous muscles relax and blood flows out of the penis. Erectile dysfunction may occur when there is insufficient blood supply to the penis or when the penis is unable to prevent outflow of blood from the penis. Sildenafil is a specific inhibitor of PDE5, an enzyme responsible for the breakdown of cGMP to 5’-GMP. Increased levels of cGMP stimulate vasodilation and facilitate the generation and maintenance of erections. These vasodilatory effects also help decrease symptoms of PAH. Sildenfail also exhibits some activity against PDE6 (10 times less potentcy compared to PDE5), a PDE isoform found predmoninantly in the retina. This activity is responsible for the blue tinged vision experienced by users of sildenafil.
Cơ Chế Tác Dụng : Sildenfail is a vasoactive agent used to treat erectile dysfunction and reduce symptoms in patients with pulmonary arterial hypertension (PAH). Sildenafil elevates levels of the second messenger, cGMP, by inhibiting its breakdown via phosphodiesterase type 5 (PDE5). PDE5 is found in particularly high concentrations in the corpus cavernosum, erectile tissue of the penis. It is also found in the retina and vascular endothelium. Increased cGMP results in vasodilation which facilitates generation and maintenance of an erection. The vasodilatory effects of sildenafil also help reduce symptoms of PAH. Sildenafil 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 sildenafil enhances erectile function by increasing the amount of cGMP.
Dược Động Học :
▧ Absorption :
>90% absorbed with ~40% reaching systemic circulation unchanged following first-pass metabolism
▧ Volume of Distribution :
* 105 L
▧ Protein binding :
96%
▧ Metabolism :
Sildenafil appears to be completely metabolized in the liver to 16 metabolites. Its metabolism is mediated mainly by cytochrome P450 microsomal isozymes 3A4 (major route) and 2C9 (minor route). The major circulating metabolite, N-demethylated metabolite, has PDE selectivity similar to the parent drug and ~50% of its in vitro potency. The N-demethylated metabolite is further metabolized to an N-dealkylated N,N-de-ethylated metabolite. Sildenafil also undergoes N-dealkylation followed by N-demethylation of the piperazine ring.
▧ Route of Elimination :
Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
▧ Half Life :
4 hours
Chỉ Định : For the treatment of erectile dysfunction and to relieve symptoms of pulmonary arterial hypertension (PAH).
Tương Tác Thuốc :
  • Amprenavir The protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil.
  • Asenapine Increased incidence of adverse effects (hypotension) due to pharmacodynamic synergism. Concomitant therapy should be avoided.
  • Atazanavir Increases the effect and toxicity of sildenafil
  • Cimetidine Increases the effect and toxicity of sildenafil
  • Ciprofloxacin Ciprofloxacin may increase the serum level of sildenafil.
  • Clarithromycin Increases the effect and toxicity of sildenafil
  • Conivaptan CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Sildenafil. When sildenanfil is used for treatment of pulmonary arterial hypertension, concurrent use with strong CYP3A4 inhibitors is not recommended. When sildenafil is used for treatment of erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking a strong CYP3A4 inhibitor. Due to the particularly strong effects of ritonavir, sildenafil (for erectile dysfunction) doses greater than 25 mg per 48 hours are not recommended. Of note, the interaction between CYP3A4 inhibitors and sildenafil is predicted to be greater with orally administered than with injected sildenafil.
  • Erythromycin The macrolide, erythromycin, may increase the effect and toxicity of sildenafil.
  • Etravirine Sildenafil (and other phosphodiesterase 5 inhibitors), when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to monitor the efficacy of sildenafil therapy.
  • Fosamprenavir The protease inhibitor, fosamprenavir, may increase the effect and toxicity of sildenafil.
  • Indinavir The protease inhibitor, indinavir, may increase the effect and toxicity of sildenafil.
  • Isosorbide Dinitrate Possible significant hypotension with this combination
  • Isosorbide Mononitrate Possible significant hypotension with this combination
  • Itraconazole Itraconazole may increase the effect and toxicity of sildenafil.
  • Ketoconazole Ketoconazole may increase the effect and toxicity of sildenafil.
  • Nelfinavir The protease inhibitor, nelfinavir, may increase the effect and toxicity of sildenafil.
  • Nitroglycerin Possible significant hypotension with this combination
  • Pentaerythritol Tetranitrate Possible significant hypotension with this combination
  • Telithromycin Telithromycin may reduce clearance of Sildenafil. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sildenafil if Telithromycin is initiated, discontinued or dose changed.
  • Terazosin Increased risk of hypotension.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the concentration of Sildenafil. Alternate therapy should be considered.
  • Vigabatrin Increased anticonvulsant effects of vigabatrin due to pharmacodynamic synergism. Monitor for adverse effects during concomitant therapy.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sildenafil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of sildenafil if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet, film coated - Oral - 100 mg
Tablet, film coated - Oral - 20 mg
Tablet, film coated - Oral - 25 mg
Tablet, film coated - Oral - 50 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Revatio 10 mg/12.5 ml vial
    Giá bán buôn : USD >9.33
    Đơn vị tính : ml
  • Biệt dược thương mại : Revatio 20 mg tablet
    Giá bán buôn : USD >17.5
    Đơn vị tính : tablet
  • Biệt dược thương mại : Viagra 100 mg tablet
    Giá bán buôn : USD >19.45
    Đơn vị tính : tablet
  • Biệt dược thương mại : Viagra 25 mg tablet
    Giá bán buôn : USD >19.45
    Đơn vị tính : tablet
  • Biệt dược thương mại : Viagra 50 mg tablet
    Giá bán buôn : USD >19.45
    Đơn vị tính : tablet
  • Biệt dược thương mại : Sildenafil citrate powder
    Giá bán buôn : USD >24.38
    Đơn vị tính : g
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Revatio
  • Công ty : Pfizer
    Sản phẩm biệt dược : Viagra
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00203
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5212
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508371
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07259
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02229
ChemSpider
http://www.chemspider.com/Chemical-Structure.5023.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=14390
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0069-4190-68
PharmGKB
http://www.pharmgkb.org/drug/PA451346
Wikipedia
http://en.wikipedia.org/wiki/Sildenafil
RxList
http://www.rxlist.com/cgi/generic/viagra.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=via1479.html&contentName=Viagra&contentId=818
Drugs.com
http://www.drugs.com/cdi/sildenafil.html
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