Tìm theo
Solifenacin
Các tên gọi khác (4 ) :
  • solifenacin succinate
  • Vesicare
  • YM-67905
  • YM-905
muscarinic antagonists, anti incontinence agents, antispasmodics
Thuốc Gốc
Small Molecule
CAS: 242478-37-1
ATC: G04BD08
ĐG : Astellas Pharma Inc. , http://www.astellas.com
CTHH: C27H32N2O6
PTK: 480.5528
Solifenacin (rINN), marketed as solifenacin succinate under the trade name Vesicare, is a urinary antispasmodic of the anticholinergic class. It is used in the treatment of overactive bladder with urge incontinence. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C27H32N2O6
Phân tử khối
480.5528
Monoisotopic mass
480.226036766
InChI
InChI=1S/C23H26N2O2.C4H6O4/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19;5-3(6)1-2-4(7)8/h1-9,18,21-22H,10-16H2;1-2H2,(H,5,6)(H,7,8)/t21-,22-;/m0./s1
InChI Key
InChIKey=RXZMMZZRUPYENV-VROPFNGYSA-N
IUPAC Name
butanedioic acid (3R)-1-azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
Traditional IUPAC Name
solifenacin; succinic acid
SMILES
OC(=O)CCC(O)=O.O=C(O[C@H]1CN2CCC1CC2)N1CCC2=CC=CC=C2[C@@H]1C1=CC=CC=C1
logP
3.96
pKa (Strongest Basic)
8.88
PSA
32.78 Å2
Refractivity
106.06 m3·mol-1
Polarizability
40.52 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.
Cơ Chế Tác Dụng : Solifenacin (rINN), marketed as solifenacin succinate under the trade name Vesicare, is a urinary antispasmodic of the anticholinergic class. It is used in the treatment of overactive bladder with urge incontinence. [Wikipedia] Solifenacin is a competitive muscarinic acetylcholine receptor antagonist. The binding of acetylcholine to these receptors, particularly the M3 receptor subtype, plays a critical role in the contraction of smooth muscle. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine and reducing the number of incontinence episodes.
Dược Động Học :
▧ Absorption :
The absolute bioavailability of solifenacin is approximately 90%, and plasma concentrations of solifenacin are proportional to the dose administered.
▧ Volume of Distribution :
* 600 L
▧ Protein binding :
Solifenacin is approximately 98% (in vivo) bound to human plasma proteins, principally to alpha1-acid glycoprotein.
▧ Metabolism :
Solifenacin is extensively metabolized in the liver. The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist. The primary metabolic routes of solifenacin are through N-oxidation of the quinuclidin ring and 4R-hydroxylation of tetrahydroisoquinoline ring. One pharmacologically active metabolite (4R-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (N-glucuronide and the N-oxide and 4R-hydroxy-N-oxide of solifenacin) have been found in human plasma after oral dosing.
▧ Route of Elimination :
The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist.
▧ Half Life :
The elimination half-life of solifenacin following chronic dosing is approximately 45-68 hours.
Độc Tính : Overdosage with solifenacin can potentially result in severe anticholinergic effects and should be treated accordingly. The highest solifenacin dose given to human volunteers was a single 100 mg dose. Intolerable anticholinergic side effects (fixed and dilated pupils, blurred vision, failure of heel-to-toe exam, tremors and dry skin) occurred on day 3 in normal volunteers taking 50 mg daily (5 times the maximum recommended therapeutic dose).
Chỉ Định : For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Tương Tác Thuốc :
  • Clarithromycin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Donepezil Possible antagonism of action
  • Galantamine Possible antagonism of action
  • Itraconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Ketoconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Nefazodone This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
  • Nelfinavir This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Solifenacin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
  • Telithromycin Telithromycin may reduce clearance of Solifenacin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Solifenacin if Telithromycin is initiated, discontinued or dose changed.
  • Trimethobenzamide Trimethobenzamide and Solifenacin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Triprolidine Triprolidine and Solifenacin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Trospium Trospium and Solifenacin, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of solifenacin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of solifenacin if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Vesicare
  • Công ty :
    Sản phẩm biệt dược : Vesikur
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01591
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=216457
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506006
ChemSpider
http://www.chemspider.com/Chemical-Structure.187603.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/51248-150-01
PharmGKB
http://www.pharmgkb.org/drug/PA164783810
Wikipedia
http://en.wikipedia.org/wiki/Solifenacin
RxList
http://www.rxlist.com/cgi/generic/vesicare.htm
Drugs.com
http://www.drugs.com/cdi/solifenacin.html
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