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药品详细

Solifenacin(索非那新)

化学结构式图
中文名
索非那新
英文名
Solifenacin
分子式
C27H32N2O6
化学名
butanedioic acid (3R)-1-azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
分子量
Average: 480.5528
Monoisotopic: 480.226036766
CAS号
242478-37-1
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

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]

生产厂家
  • Astellas pharma us inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenethylamines
  • (Iso)quinolines and Derivatives
Substructures
  • Hydroxy Compounds
  • Acetates
  • Carbamates and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Keto-Acids
  • Piperidines
适应症
药理
Indication For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Pharmacodynamics 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.
Mechanism of action 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.
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Solifenacin
    		4R-hydroxy solifenacin Details
    Solifenacin
      		4R-hydroxy-N-oxide solifenacin Details
      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.
      Clearance Not Available
      Toxicity 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).
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      理化性质
      Properties
      State solid
      Experimental Properties Not Available
      Predicted Properties
      Property Value Source
      logP 3.96 ChemAxon
      pKa (strongest basic) 8.88 ChemAxon
      physiological charge 1 ChemAxon
      hydrogen acceptor count 2 ChemAxon
      hydrogen donor count 0 ChemAxon
      polar surface area 32.78 ChemAxon
      rotatable bond count 6 ChemAxon
      refractivity 106.06 ChemAxon
      polarizability 40.52 ChemAxon
      药物相互作用
      Drug Interaction
      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.
      食物相互作用
      Not Available

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