Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H26N2O2.C4H6O4 |
Molecular Weight | 480.5528 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CCC(O)=O.O=C(O[C@H]1CN2CCC1CC2)N3CCC4=CC=CC=C4[C@@H]3C5=CC=CC=C5
InChI
InChIKey=RXZMMZZRUPYENV-VROPFNGYSA-N
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
DescriptionCurator's Comment: description was created based on several sources, including:
http://www.rxlist.com/vesicare-drug.htm
https://www.drugs.com/mtm/solifenacin.html
http://www.wikidoc.org/index.php/Solifenacin
Curator's Comment: description was created based on several sources, including:
http://www.rxlist.com/vesicare-drug.htm
https://www.drugs.com/mtm/solifenacin.html
http://www.wikidoc.org/index.php/Solifenacin
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. It is FDA approved for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Common adverse reactions include constipation, Xerostomia. Inhibitors of CYP3A4 may increase the concentration of Solifenacin. Vice versa, CYP3A4 Inducers decrease concentration.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23094215 http://www.ics.org/Abstracts/Publish/46/000185.pdf
Curator's Comment: Known to be CNS penetrant in rat. Human data not available
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL245 |
10.0 nM [Ki] | ||
125.0 nM [Ki] | |||
25.0 nM [Ki] | |||
7.73 null [pKi] | |||
7.46 null [pKi] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VESICARE Approved UseVESIcare is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. VESIcare is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency (1) Launch Date2004 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986 |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
SOLIFENACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
820 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986 |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
SOLIFENACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
50.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15206986 |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
SOLIFENACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
SOLIFENACIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: Page: p.1028 |
healthy, 19-40 n = 6 Health Status: healthy Age Group: 19-40 Sex: M Population Size: 6 Sources: Page: p.1028 |
|
30 mg 1 times / day multiple, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: Page: p.1029 |
healthy, 20-35 n = 8 Health Status: healthy Age Group: 20-35 Sex: M Population Size: 8 Sources: Page: p.1029 |
|
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.4 |
unhealthy n = 1233 Health Status: unhealthy Condition: Overactive bladder Population Size: 1233 Sources: Page: p.4 |
Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (1.5%) Sources: Page: p.4 |
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
Disc. AE: Angioedema, Anaphylactic reaction... AEs leading to discontinuation/dose reduction: Angioedema Sources: Page: p.1Anaphylactic reaction (rare) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dry mouth | 1.5% Disc. AE |
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.4 |
unhealthy n = 1233 Health Status: unhealthy Condition: Overactive bladder Population Size: 1233 Sources: Page: p.4 |
Angioedema | Disc. AE | 10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
Anaphylactic reaction | rare Disc. AE |
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
not significant | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_biopharmr.pdf#page=51 Page: 51.0 |
yes [Inhibition 1.04 uM] |
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-518_VESIcare_pharmr.pdf#page=35 Page: 35.0 |
PubMed
Title | Date | PubMed |
---|---|---|
M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. | 2002 Aug |
|
Gateways to clinical trials. | 2003 Jul-Aug |
|
Gateways to clinical trials. | 2003 Jun |
|
Gateways to clinical trials. | 2003 Nov |
|
Gateways to clinical trials. | 2004 Dec |
|
Gateways to clinical trials. | 2004 Nov |
|
Elevating our therapeutic expectations in overactive bladder. | 2004 Oct |
|
Preview of new drugs for overactive bladder and incontinence: darifenacin, solifenacin, trospium, and duloxetine. | 2004 Oct |
|
The emerging role of solifenacin in the treatment of overactive bladder. | 2004 Oct |
|
Pharmacokinetics and safety of solifenacin succinate in healthy young men. | 2004 Sep |
|
Solifenacin in overactive bladder: a viewpoint by Hashim Hashim. | 2005 |
|
[Neurological aspect of the hyperactive urinary bladder syndrome]. | 2005 |
|
Improving the tolerability of anticholinergic agents in the treatment of overactive bladder. | 2005 |
|
New molecular entity: Vesicare, Yamanouchi/GlaxoSmithKline solifenacin. | 2005 Jan |
|
Improved quality of life in patients with overactive bladder symptoms treated with solifenacin. | 2005 Jan |
|
[Medical therapy of urinary incontinence]. | 2005 Jan |
|
Darifenacin in the treatment of overactive bladder. | 2005 Jul |
|
New treatment options for overactive bladder. | 2005 Jun |
|
Effect of age on the pharmacokinetics of solifenacin in men and women. | 2005 May |
|
[Drug discovery in the fields of urology: tamsulosin and solifenacin]. | 2005 Nov |
|
Solifenacin versus tolterodine--a head-to-head study: finally! But not final? | 2005 Nov |
|
Role of muscarinic receptor antagonists in urgency and nocturia. | 2005 Sep |
|
Gateways to clinical trials. | 2006 Apr |
|
The causes and consequences of overactive bladder. | 2006 Apr |
|
New developments in the treatment of urinary incontinence. | 2006 Dec |
|
Solifenacin succinate (VESIcare): overactive bladder therapy. | 2006 Dec |
|
Open-label study of the safety and pharmacokinetics of solifenacin in subjects with hepatic impairment. | 2006 Dec |
|
Solifenacin provides effective antimuscarinic therapy for the complete management of overactive bladder. | 2006 Dec |
|
Muscarinic receptors in the bladder: from basic research to therapeutics. | 2006 Feb |
|
Pharmacokinetic effect of ketoconazole on solifenacin in healthy volunteers. | 2006 Jul |
|
[Comment on the STAR study: Comparison of the efficacy and tolerance of solifenacin and tolterodine retard in the treatment of overactive bladder]. | 2006 Jul |
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[Oral anticholinergics in overactive bladder]. | 2006 Jul |
|
Gateways to clinical trials. | 2006 Jul-Aug |
|
Short- and long-term efficacy of solifenacin treatment in patients with symptoms of mixed urinary incontinence. | 2006 Jun |
|
Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. | 2006 Mar |
|
The emergence of new drugs for overactive bladder. | 2006 Mar |
|
Management of overactive bladder and urge urinary incontinence in the elderly patient. | 2006 Mar |
|
Gateways to clinical trials. | 2006 May |
|
Symptom bother and health-related quality of life outcomes following solifenacin treatment for overactive bladder: the VESIcare Open-Label Trial (VOLT). | 2006 Nov |
|
Gateways to clinical trials. | 2006 Nov |
|
Solifenacin. | 2006 Nov |
|
Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: A pooled analysis. | 2006 Sep |
|
Reductions in overactive bladder-related incontinence from pooled analysis of phase III trials evaluating treatment with solifenacin. | 2006 Sep |
|
Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test. | 2007 Feb 28 |
|
Pharmacokinetics, safety, and tolerability of solifenacin in patients with renal insufficiency. | 2007 Jan |
|
Redefining response in overactive bladder syndrome. | 2007 Jan |
|
Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents. | 2007 Jan |
|
Solifenacin for overactive bladder with incontinence: symptom bother and health-related quality of life outcomes. | 2007 Mar |
|
An unusual cause of postoperative detrusor overactivity. | 2007 Oct |
|
Comparison of the efficacy and tolerability of solifenacin succinate with or without previous use of trospium chloride. | 2007 Sep |
Patents
Sample Use Guides
5 mg tablet taken once daily, and if well tolerated may be increased to 10 mg once daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15178371
The inhibitory effect of solifenacin (dose range: 10^-10 - 10^-6 M) for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57).
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29704
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C73805
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KKA5DLD701
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m10108
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SUB21028
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242478-38-2
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CHEMBL1734
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD