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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/18 13:50:52」(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^[1] with associated problems such as increased urination frequency and urge incontinence.^[2] It is manufactured and marketed by Astellas, GlaxoSmithKline^[3] and Teva Pharmaceutical Industries.^{[citation needed]}

Contraindications

Solifenacin is contraindicated for people with urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, severe liver disease (Child-Pugh class C),^[4] and hemodialysis.^[2]

Long QT syndrome is not a contraindication although solifenacin, like tolterodine and darifenacin, binds to hERG channels of the heart and may prolong the QT interval. This mechanism appears to be seldom clinically relevant.^[5]

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.^[4]

Interactions

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.^[4]

As stated above, solifenacin may also prolong the QT interval. Therefore, administering it concomitantly with drugs which also have this effect, such as moxifloxacin or pimozide, can theoretically increase the risk of arrhythmia.^[3]

Pharmacology

Mechanism of action

Solifenacin is a competitive cholinergic receptor antagonist, selective for the M₃ receptor subtype. The binding of acetylcholine to these receptors, particularly M₃, 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.^[2]

Pharmacokinetics

Peak plasma concentrations are reached 3 to 8 hours after absorption from the gut. In the bloodstream, 98% of the substance are bound to plasma proteins, mainly acidic ones. Metabolism is mediated by the liver enzyme CYP3A4 and possibly others. There is one known active metabolite, 4R-hydroxysolifenacin, and three inactive ones, the N-glucuronide, the N-oxide and the 4R-hydroxy-N-oxide. The elimination half-life is 45 to 68 hours. 69% of the substance, both in its original form and as metabolites, are excreted renally and 23% via the feces.^[2]

Physical and chemical properties

Atropine for comparison

Like other anticholinergics, solifenacin is an ester of a carboxylic acid containing (at least) an aromatic ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergic atropine the alcohol is tropine, solifenacin has another bicycle, quinuclidinyl alcohol.

The substance is a basic yellow oil, while the form used in tablets, solifenacin succinate, consists of white to slightly yellowish crystals.^[6]

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.^[7]

Society and culture

Economics

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.^[8]

References

^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 343. ISBN 1437727883.
^ ^a ^b ^c ^d Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8659–62. ISBN 978-3-85200-181-4.
^ ^a ^b Drugs.com: monograph on Vesicare.
^ ^a ^b ^c Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional. Retrieved 10 June 2011.
^ "Vesicare 5mg & 10mg film-coated tablets". eMC. Retrieved 13 December 2015.
^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals (14 ed.). 2006. p. 1494. ISBN 978-0-911910-00-1.
^ 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.
^ 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.

UpToDate Contents

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1. 女性における尿失禁の治療および予防 treatment and prevention of urinary incontinence in women
2. 男性における下部尿路症状 lower urinary tract symptoms in men
3. 夜間頻尿：臨床症状、診断、および治療治療 nocturia clinical presentation diagnosis and treatment
4. 男性の尿失禁 urinary incontinence in men
5. 小児における膀胱機能障害のマネージメント management of bladder dysfunction in children

English Journal

A critical assessment of the effects of tamsulosin and solifenacin as monotherapies and as a combination therapy for the treatment of ureteral stent-related symptoms: a 2 × 2 factorial randomized trial.

Park J1, Yoo C2, Han DH3, Shin DW4.
World journal of urology.World J Urol.2015 Nov;33(11):1833-40. doi: 10.1007/s00345-015-1544-1. Epub 2015 Mar 26.
OBJECTIVE: To assess the efficacy of tamsulosin, solifenacin, and combination therapy of both agents for the treatment of ureteral stent-related symptoms (SRSs).METHODS: An open-label, randomized controlled trial was conducted with 112 patients who underwent unilateral ureteral stent insertion follo
PMID 25809877

Potentially inappropriate anticholinergic medication use in older adults with dementia.

Kachru N, Carnahan RM, Johnson ML, Aparasu RR.
Journal of the American Pharmacists Association : JAPhA.J Am Pharm Assoc (2003).2015 Oct 24:e475-e484. doi: 10.1331/JAPhA.2015.14288. [Epub ahead of print]
Objective: To examine the prevalence and predictors of potentially inappropriate anticholinergic medication use in older adults with dementia.Design: A cross-sectional study.Setting: United States, 2009-2010.Participants: Medical Expenditure Panel Survey household component participants aged 65 year
PMID 26501745

Impact of Loss of Work Productivity in Patients with Overactive Bladder Treated with Antimuscarinics in Spain: Study in Routine Clinical Practice Conditions.

Sicras-Mainar A1, Navarro-Artieda R2, Ruiz-Torrejón A3, Sáez-Zafra M4, Coll-de Tuero G5.
Clinical drug investigation.Clin Drug Investig.2015 Oct 13. [Epub ahead of print]
BACKGROUND: Overactive bladder (OAB) is a syndrome characterized by presenting symptoms of urgency, with or without urge incontinence, and normally accompanied by day and night frequency.OBJECTIVE: The aim of this study was to evaluate the impact of lost work productivity [number of days of sick lea
PMID 26464261

Japanese Journal

味覚センサを用いた医薬品の服用性の総合評価

YAKUGAKU ZASSHI 134(3), 317-323, 2014
NAID 130003391169

DDS製品開発の最前線(23)ベシケアOD錠口腔内で崩壊するのに苦くない

Drug delivery system : DDS : official journal of the Japan Society of Drug Delivery System 28(5), 452-457, 2013-11
NAID 40019894033

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

有機合成化学協会誌 70(10), 1011-1017, 2012-10-01
NAID 10031124006

Related Pictures

Vesicare - 100% SANTÉ BEAUTÉ FORME VESICARE tbl 30x 10mg Vesicare - Buy Incontinence Tablets Online Vesicare - lek skutecznie zwiększający Vesicare | Solifenacin | Bad Drug Vesicare – Effective Treatment For werkzame stof (= solifenacine) in Vesicare VESICARE (solifenacin succinate) 5mg, 10mg

★リンクテーブル★

リンク元

「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: POM (Prescription only); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	90%
Protein binding	98%
Metabolism	CYP3A4
Metabolites	Glucuronide, N-oxide, others
Biological half-life	45 to 68 hours
Excretion	Renal (69.2%) and fecal (22.5%)
Identifiers
CAS Number	242478-37-1
ATC code	G04BD08
PubChem	CID: 154059
IUPHAR/BPS	7483
DrugBank	DB01591
ChemSpider	135771
UNII	A8910SQJ1U
KEGG	DG00481
ChEMBL	CHEMBL1734
Synonyms	YM905
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

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

[Austria-Codex-2] Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8659–62. ISBN 978-3-85200-181-4.

[Drugs.com-3] Drugs.com: monograph on Vesicare.

[Lexi-Comp-4] Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional. Retrieved 10 June 2011.

[5] "Vesicare 5mg & 10mg film-coated tablets". eMC. Retrieved 13 December 2015.

[MerckIndex-6] The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals (14 ed.). 2006. p. 1494. ISBN 978-0-911910-00-1.

[7] 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.

[8] 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.

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Vesicare