Tìm theo
Silodosin
Các tên gọi khác (4 ) :
  • KAD 3213
  • KMD 3213
  • Rapaflo
  • Urief
adrenergic alpha 1 receptor antagonists
Thuốc Gốc
Small Molecule
CAS: 160970-54-7
ATC: G04CA04
CTHH: C25H32F3N3O4
PTK: 495.5345
Silodosin is an α1-adrenoceptor antagonist that is selective for the prostate. Silodosin is for symptomatic treatment of benign prostatic hyperplasia. FDA approved Oct 9, 2008.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C25H32F3N3O4
Phân tử khối
495.5345
Monoisotopic mass
495.234491142
InChI
InChI=1S/C25H32F3N3O4/c1-17(30-8-12-34-21-5-2-3-6-22(21)35-16-25(26,27)28)13-18-14-19-7-10-31(9-4-11-32)23(19)20(15-18)24(29)33/h2-3,5-6,14-15,17,30,32H,4,7-13,16H2,1H3,(H2,29,33)/t17-/m1/s1
InChI Key
InChIKey=PNCPYILNMDWPEY-QGZVFWFLSA-N
IUPAC Name
1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide
Traditional IUPAC Name
silodosin
SMILES
C[C@H](CC1=CC2=C(N(CCCO)CC2)C(=C1)C(N)=O)NCCOC1=CC=CC=C1OCC(F)(F)F
Độ tan chảy
105 - 109°C
Độ hòa tan
Very slightly soluble
logP
3.05
logS
-4.7
pKa (strongest acidic)
14.87
pKa (Strongest Basic)
9.66
PSA
97.05 Å2
Refractivity
128.92 m3·mol-1
Polarizability
49.89 Å3
Rotatable Bond Count
14
H Bond Acceptor Count
6
H Bond Donor Count
3
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Silodosin is 583 times more selective for human alpha-1A receptors than alpha-1B receptors. It is also 56 times more selective for human alpha-1A receptors than alpha-1D. Silodosin does not prolong the QT interval.
Cơ Chế Tác Dụng : Silodosin is an α1-adrenoceptor antagonist that is selective for the prostate. Silodosin is for symptomatic treatment of benign prostatic hyperplasia. FDA approved Oct 9, 2008. Benign prostate hyperplasia (BPH), or an enlarged prostate, is a condition found only in men and is characterized by a non-cancerous enlargement of the prostate gland. Symptoms of BPH include urinary difficulty, urinary frequency and an inability to complete bladder emptying. Silodosin is highly uroselective for the alpha (1A) receptors located in the prostate, [urethrea and bladder trigone in the lower urinary tract]. Blocking these receptors relaxes the smooth muscles, resulting in an improvement in urine flow and a reduction in BPH symptoms. The selective binding of silodosin to the alpha (1A) receptors is substantially greater than the binding to the cardiovascular-associated alpha (1B) receptors and thereby maximizes target organ activity while minimizing the potential for blood pressure effects. [Watson Pharmaceutical Inc. Press release] Silodosin is alpha 1A-adrenoceptor selective antagonist which inhibits sympathetic nerve stimulation and relaxation of smooth muscle tone in the lower urinary tract which relieves the pressure from contraction of smooth muscle. The reduction of intraurethral pressure improves voiding and storage issues associated with BPH.
Dược Động Học :
▧ Absorption :
Quickly absorbed and has a bioavailability of 32% at 8mg/day (therapeutic dose). When 8 mg of silodosin is taken once daily with food, the pharmacokinetic parameters are as follows: Cmax = 61.6 ± 27.54 ng/mL; Tmax = 2.6 ± 0.90 hours; AUC (0h-24h) = 373 ng•hr/ml. The AUC of its metabolite, KMD3213G, is four times greater than silodosin.
▧ Volume of Distribution :
49.5 L
▧ Protein binding :
97% bound to protein
▧ Metabolism :
Extensively metabolized in the liver. The main metabolite is generated via glucuronidation (KMD-3213G) by UDP-2B7. Oxidation by alcohol and aldehyde dehydrogenases produces the second major metabolite, KMD-3293. KMD-3213G accumulates in the plasma as it is very hydrophilic. KMD-3213G is also an active metabolite in which it has 50% of silodosin's inhibitory activity. KMD-3293 is inactive. Cytochrome P450 CYP 3A4 also generates some metabolites.
▧ Route of Elimination :
Fecal (54.9%); Renal (33.5%)
▧ Half Life :
Silodosin = 13.3 ± 8.07 hours; KMD-3213G = 24 hours;
▧ Clearance :
Plasma clearance = 10 L/h
Độc Tính : Most common adverse reactions (incidence > 2%) are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.
Chỉ Định : Treatment for symptomatic relief of benign prostatic hyperplasia
Tương Tác Thuốc :
  • Chloramphenicol Chloramphenicol is a strong inhibitor of CYP3A4 may increase the serum concentration of silodosin by decreasing its metabolism thus increases the potential for adverse side effects. Combination therapy is contraindicated.
  • Conivaptan CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Silodosin. Use of silodosin concomitantly with a strong CYP3A4 inhibitor is contraindicated.
  • Diltiazem Moderate inhibitors of CYP3A4 may increase levels of silodosin. Monitor concomitant therapy closely.
  • Erythromycin Erythromycin is a moderate inhibitor of CYP3A4 and inhibits P-glycoprotein thus increasing the potential for adverse effects
  • Fluconazole Strong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
  • Indinavir Indinavir is a strong inhibitor of CYP3A4 may increase the serum concentration of silodosin by decreasing its metabolism thus increases the potential for adverse side effects. Combination therapy is contraindicated.
  • Itraconazole Strong CYP3A4 inhibitors may increase levels of silodosin. Concomitant administration is contraindicated.
  • Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of silodosin by decreasing its metabolism thus increases the potential for adverse side effects
  • Probenecid Strong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
  • Ritonavir Strong CYP3A4 inhibitors may increase levels of silodosin. Concomitant administration is contraindicated.
  • Tacrolimus The p-glycoprotein inhibitor, Tacrolimus, may increase the bioavailability of Silodosin. Increased Silodosin exposure may result in Silodosin toxicity. Concurrent use if not recommended.
  • Tamsulosin Additive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy is not recommended.
  • Terazosin Additive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy should be avoided.
  • Valproic Acid Strong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
  • Vardenafil Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Silodosin, may occur. Monitor for hypotension during concomitant therapy.
  • Verapamil Verapamil is a moderate inhibitor of CYP3A4 and inhibits P-glycoprotein thus increasing the potential for adverse effects
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of silodosin by decreasing its metabolism. Concomitant therapy is contraindicated.
Liều Lượng & Cách Dùng : Capsule - Oral - 4 mg
Capsule - Oral - 8 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06207
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5312125
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=7849027
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01965
ChemSpider
http://www.chemspider.com/Chemical-Structure.4471557.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50160154
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/54868-6173-0
PharmGKB
http://www.pharmgkb.org/drug/PA165291889
Wikipedia
http://en.wikipedia.org/wiki/Silodosin
RxList
http://www.rxlist.com/rapaflo-capsules-drug.htm
Drugs.com
http://www.drugs.com/cdi/silodosin.html
... loading
... loading