FLAVOXATE

First approved in 1970

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H25NO4
Molecular Weight	391.4596
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(OC2=C(C=CC=C2C(=O)OCCN3CCCCC3)C1=O)C4=CC=CC=C4

InChI

InChIKey=SPIUTQOUKAMGCX-UHFFFAOYSA-N

InChI=1S/C24H25NO4/c1-17-21(26)19-11-8-12-20(23(19)29-22(17)18-9-4-2-5-10-18)24(27)28-16-15-25-13-6-3-7-14-25/h2,4-5,8-12H,3,6-7,13-16H2,1H3

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9c44c4b-5b3c-45bf-9bc9-ce858e3d06c5 | https://livertox.nlm.nih.gov/Flavoxate.htm

Flavoxate is a drug, indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. Flavoxate is not indicated for definitive treatment, but is compatible with drugs used for the treatment of urinary tract infections. It was approved for use in the United States in 1970 and continues to be used. Drug acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, facilitating increased volume per void. Common side effects are those of parasympathetic stimulation and include dryness of the mouth and eyes, decreased sweating, headache, visual blurring, constipation, urinary retention, impotence, tachycardia and palpitations, anxiety, restlessness and in some instances agitation and delusions.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptors; M1 & M2 2 Target ID: CHEMBL2095219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10858873	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Cystitis 27 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9c44c4b-5b3c-45bf-9bc9-ce858e3d06c5	Palliative	Approved 8429	FLAVOXATE HYDROCHLORIDE Approved Use Flavoxate HCl tablets are indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. Flavoxate HCl tablets are not indicated for definitive treatment, but are compatible with drugs used for the treatment of urinary tract infections. Launch Date 1.10315517E12
Prostatitis 25 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9c44c4b-5b3c-45bf-9bc9-ce858e3d06c5	Palliative	Approved 8429	FLAVOXATE HYDROCHLORIDE Approved Use Flavoxate HCl tablets are indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. Flavoxate HCl tablets are not indicated for definitive treatment, but are compatible with drugs used for the treatment of urinary tract infections. Launch Date 1.10315517E12
Urethritis 18 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9c44c4b-5b3c-45bf-9bc9-ce858e3d06c5	Palliative	Approved 8429	FLAVOXATE HYDROCHLORIDE Approved Use Flavoxate HCl tablets are indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. Flavoxate HCl tablets are not indicated for definitive treatment, but are compatible with drugs used for the treatment of urinary tract infections. Launch Date 1.10315517E12

C_max

Value	Dose	Co-administered	Analyte	Population
4.61 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1026965	1.18 mg/kg single, intravenous dose: 1.18 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
14.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11232858/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
4.02 mg × h/L/(mg dose/kg) EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1026965	2.55 mg/kg single, oral dose: 2.55 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.49 mg × h/L/(mg dose/kg) EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1026965	1.18 mg/kg single, intravenous dose: 1.18 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.85 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11232858/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
40.1 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1026965	1.18 mg/kg single, intravenous dose: 1.18 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.06 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11232858/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		3-METHYLFLAVONE-8-CARBOXYLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 3 times / day multiple, oral Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348	unhealthy, 26 years n = 1 Health Status: unhealthy Condition: urinary infection Age Group: 26 years Sex: F Population Size: 1 Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348	Disc. AE: Erythema, Edema hands... AEs leading to discontinuation/dose reduction: Erythema Edema hands Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348
1200 mg 1 times / day multiple, oral Dose: 1200 mg, 1 times / day Route: oral Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3044876	unhealthy, 49.8 ± 9.7 years Health Status: unhealthy Condition: unstable bladder Age Group: 49.8 ± 9.7 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3044876	Sources: https://pubmed.ncbi.nlm.nih.gov/3044876

AEs

AE	Significance	Dose	Population
Edema hands	Disc. AE	200 mg 3 times / day multiple, oral Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348	unhealthy, 26 years n = 1 Health Status: unhealthy Condition: urinary infection Age Group: 26 years Sex: F Population Size: 1 Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348
Erythema	Disc. AE	200 mg 3 times / day multiple, oral Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348	unhealthy, 26 years n = 1 Health Status: unhealthy Condition: urinary infection Age Group: 26 years Sex: F Population Size: 1 Sources: http://www.jiaci.org/issues/vol22issue5/8-20.pdf https://pubmed.ncbi.nlm.nih.gov/10385348

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 MRP1 106 BCRP 699	CYP 270

Drug as perpetrator

Target	Modality	Activity
MRP1 172	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711991/	weak
P-gp 1650	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711991/	weak
BCRP 773	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711991/	yes [IC50 20 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906583/#B5	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5088	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5088
ChemicalBook	CB2341499	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2341499
ZINC	ZINC000000608382	http://zinc15.docking.org/substances/ZINC000000608382
eMolecules	736698	https://www.emolecules.com/cgi-bin/more?vid=736698

PubMed

Title	Date	PubMed
Association between oxybutynin and neuropsychiatric adverse effects not confirmed in daily practice.	2001 Feb	11207885
Incorrect assumption regarding the mechanism of action of flavoxate.	2002 Feb	12028232
Urinary antispasmodic use and the risks of ventricular arrhythmia and sudden death in older patients.	2002 Jan	12028256
Bladder training for urinary incontinence in adults.	2004	14973967
[Alpha-blockers and bioflavonoids in men with chronic nonbacterial prostatitis (NIH-IIIa): a prospective, placebo-controlled trial].	2004 Feb	15132876
Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the california medicaid program.	2005 Jul-Aug	16091027
Trospium chloride: an update on a quaternary anticholinergic for treatment of urge urinary incontinence.	2005 Jun	18360555
Conformational evaluation and detailed 1H and 13C NMR assignments of flavoxate, a urinary tract antispasmodic agent.	2006 May 3	16426792
Drug-induced acute cholestatic liver damage in a patient with mutation of UGT1A1.	2007 Jul	17607296
High performance liquid chromatographic determination of 3-methylflavone-8-carboxylic acid, the main active metabolite of flavoxate hydrochloride in human urine.	2007 May 9	17349765
Effects of flavoxate hydrochloride on voltage-dependent Ba2+ currents in human detrusor myocytes at different experimental temperatures.	2007 Nov	17909749
Anticholinergic drugs versus other medications for overactive bladder syndrome in adults.	2007 Oct 17	17943782
3-Methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylic acid.	2008 Apr 16	21202344
Liquid chromatographic fingerprint of 3-methylflavone-8-carboxylic acid established for its synthesis control analysis.	2009 Mar 15	19159766
Acute myocardial infarction and Kounis syndrome.	2009 May 15	18378025
Oxybutynin extended release for the management of overactive bladder: a clinical review.	2009 Sep 21	19920931
Liquid Chromatographic Determination of Flavoxate HCl in Pharmaceutical Formulation.	2010 Jul	21042486
[Urinary incontinence and puppy coat due to spaying in the bitch. An overview of pathophysiology, diagnosis and therapy].	2010 Jun 8	22290549
New insights into molecular targets for urinary incontinence.	2010 Oct	21206614

Patents

Sample Use Guides

In Vivo Use Guide

Adults and children over 12 years of age: one or two 100 mg tablets 3 or 4 times a day. With improvement of symptoms, the dose may be reduced. This drug cannot be recommended for infants and children under 12 years of age because safety and efficacy have not been demonstrated in this age group.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

FLAVOXATE

Official Name

English

FLAVOXATE [MI]

Common Name

English

BLADURIL

Brand Name

English

Flavoxate [WHO-DD]

Common Name

English

4H-1-BENZOPYRAN-8-CARBOXYLIC ACID, 3-METHYL-4-OXO-2-PHENYL-, 2-(1-PIPERIDINYL)ETHYL ESTER

Common Name

English

2-PIPERIDINOETHYL 3-METHYL-4-OXO-2-PHENYL-4H-1-BENZOPYRAN-8-CARBOXYLATE

Systematic Name

English

FLAVOXATE [VANDF]

Common Name

English

flavoxate [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

G04BD02