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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/17 16:55:50」(JST)

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Solifenacin (INN, trade name Vesicare) is a medicine of the antimuscarinic class and was developed for treating contraction of overactive bladder with^[1] urge incontinence. It is manufactured and marketed by Astellas, Teva Pharmaceutical Industries and GlaxoSmithKline

Pharmacology

Mechanism of action

Solifenacin is a competitive cholinergic 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 micturition, urgency and incontinence episodes. Because of a long elimination half life, a once-a-day dose can offer 24-hour control of the urinary bladder smooth muscle tone.

Contraindications

Solifenacin should not be taken by people with a history of previous hypersensitivity to it, urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, or severe liver disease (Child-Pugh class C).^[2] It is also contraindicated in long QT syndrome, as solifenacin, like tolterodine and darifenacin, binds to HERG channels and may prolong the QT interval.

Medical uses

Solifenacin is metabolized in the liver by the cytochrome P450 enzyme CYP3A4. When administered concomitantly with drugs that inhibit CYP3A4, such as ketoconazole, the metabolism of solifenacin is impaired, leading to an increase in its concentration in the body and a reduction in its excretion. The manufacturer recommends that the dosage of solifenacin not exceed 5 mg a day if it is taken with a potent CYP3A4 inhibitor.^[2]

As stated above, solifenacin may also prolong the QT interval. Therefore, it should not be administered concomitantly with drugs which also have this effect, such as moxifloxacin or pimozide.

Side effects

The most common side effects of solifenacin are dry mouth, blurred vision, and constipation. As all anticholinergics, solifenacin may rarely cause hyperthermia due to decreased perspiration.^[2]

Pharmacoeconomics

A 2006 cost-effectiveness study found that 5 mg solifenacin had the lowest cost and highest effectiveness among anticholinergic drugs used to treat overactive bladder in the United States, with an average medical cost per successfully treated patient of $6863 per year.^[3]

History

The compound was studied using animal models by the Yamanouchi Pharmaceutical Co., Ltd. of Tokyo, Japan. It was known as YM905 when under study in the early 2000s. ^[4]

References

^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 343. ISBN 1437727883.
^ ^a ^b ^c Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional. Retrieved on June 10, 2011.
^ Ko Y, Malone DC, Armstrong EP (Dec 2006). "Pharmacoeconomic evaluation of antimuscarinic agents for the treatment of overactive bladder". Pharmacotherapy 26 (12): 1694–702. doi:10.1592/phco.26.12.1694. PMID 17125433.
^ Kobayashi, S. et al. (July 2001). "Effects of YM905, a Novel Muscarinic M3-Receptor Antagonist, on Experimental Models of Bowel Dysfunction In Vivo". Jpn. J. Pharmacol 86 (3): 281 – 288. PMID 11488427.

UpToDate Contents

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English Journal

The characteristics of intrinsic complex micro-contractile activity in isolated strips of the rat bladder.

Gillespie JI1, Rouget C, Palea S, Granato C, Birder L, Korstanje C.
Naunyn-Schmiedeberg's archives of pharmacology.Naunyn Schmiedebergs Arch Pharmacol.2015 Jul;388(7):709-18. doi: 10.1007/s00210-015-1131-4. Epub 2015 May 26.
The present study was done to explore the cholinergic systems operating in the wall of the isolated rat bladder. In a first set of experiments, bladder strips in vitro were subjected to cumulative concentration-response curve (CRC) to non-selective muscarine agonist carbachol or the partially M2 &
PMID 26004385

The actions of prolonged exposure to cholinergic agonists on isolated bladder strips from the rat.

Gillespie JI1, Rouget C, Palea S, Korstanje C.
Naunyn-Schmiedeberg's archives of pharmacology.Naunyn Schmiedebergs Arch Pharmacol.2015 Jul;388(7):737-47. doi: 10.1007/s00210-015-1129-y. Epub 2015 May 17.
The present study was done to explore the cholinergic systems operating in the wall of the isolated rat bladder. In a first set of experiments, bladder strips in vitro were subjected to cumulative concentration-response curve (CRC) to non-selective muscarine agonist carbachol or the partially M2>
PMID 25980359

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

Oelke M1, Becher K2, Castro-Diaz D3, Chartier-Kastler E4, Kirby M5, Wagg A6, Wehling M7.
Age and ageing.Age Ageing.2015 Jun 23. pii: afv077. [Epub ahead of print]
AIM: we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification.METHODS: to evaluate the efficacy,
PMID 26104505

Japanese Journal

過活動膀胱（OAB）治療剤ソリフェナシンの研究開発と工業化

内藤良
有機合成化学協会誌 70(10), 1011-1017, 2012
… Solifenacin succinate (Vesicare®), a novel muscarinic receptor antagonist for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency, has been approved in more than 60 countries. …
NAID 130002143024

女性過活動膀胱(OAB)患者における抗コリン剤の臨床比較検討

森光浩,久松浩,山下修史,犬塚周
西日本泌尿器科 73(11), 583-588, 2011-11-20
NAID 10030440180

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction : Ameliorative Effect of Solifenacin Succinate (Vesicare^【○!R】), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

OHTAKE Akiyoshi,SATO Shuichi,SASAMATA Masao,MIYATA Keiji
Journal of pharmacological sciences 112(2), 135-141, 2010-02-20
NAID 10029888575

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★リンクテーブル★

リンク元	「ソリフェナシン」
関連記事	「succinate」

「ソリフェナシン」

Solifenacin
Systematic (IUPAC) name
	1-azabicyclo[2.2.2]oct-3-yl (1R)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
Clinical data
Trade names	Vesicare
AHFS/Drugs.com	monograph
MedlinePlus	a605019
Licence data	US FDA:link
Pregnancy; category	AU: B3; US: C (Risk not ruled out);
Legal status	UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	90%
Protein binding	98%
Biological half-life	45 to 68 hours
Excretion	Renal (69.2%) and fecal (22.5%)
Identifiers
CAS Registry Number	242478-37-1
ATC code	G04BD08
PubChem	CID: 154059
IUPHAR/BPS	7483
DrugBank	DB01591
ChemSpider	135771
UNII	A8910SQJ1U
ChEMBL	CHEMBL1734
Chemical data
Formula	C23H26N2O2
Molecular mass	362.465 g/mol
	SMILES C1CN2CCC1[C@H](C2)OC(=O)N3CCC4=CC=CC=C4[C@@H]3C5=CC=CC=C5 ;
	InChI InChI=1S/C23H26N2O2/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/h1-9,18,21-22H,10-16H2/t21-,22-/m0/s1 ; Key:FBOUYBDGKBSUES-VXKWHMMOSA-N ;
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　　[★]

英: solifenacin
化: コハク酸ソリフェナシン, solifenacin succinate
商: ベシケア Vesicare

過敏性膀胱治療薬;平滑筋弛緩;M3受容体遮断

「succinate」

　　[★] コハク酸、コハク酸塩、コハク酸エステル, succinic acid

[Cecil-1] Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 343. ISBN 1437727883.

[Lexi-Comp-2] Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional. Retrieved on June 10, 2011.

[3] Ko Y, Malone DC, Armstrong EP (Dec 2006). "Pharmacoeconomic evaluation of antimuscarinic agents for the treatment of overactive bladder". Pharmacotherapy 26 (12): 1694–702. doi:10.1592/phco.26.12.1694. PMID 17125433.

[4] Kobayashi, S. et al. (July 2001). "Effects of YM905, a Novel Muscarinic M3-Receptor Antagonist, on Experimental Models of Bowel Dysfunction In Vivo". Jpn. J. Pharmacol 86 (3): 281 – 288. PMID 11488427.

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solifenacin succinate