ALFUZOSIN HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H27N5O4.ClH
Molecular Weight	425.91
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=CC2=NC(=NC(N)=C2C=C1OC)N(C)CCCNC(=O)C3CCCO3

InChI

InChIKey=YTNKWDJILNVLGX-UHFFFAOYSA-N

InChI=1S/C19H27N5O4.ClH/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-13-11-16(27-3)15(26-2)10-12(13)17(20)23-19;/h10-11,14H,4-9H2,1-3H3,(H,21,25)(H2,20,22,23);1H

HIDE SMILES / InChI

Molecular Formula	C19H27N5O4
Molecular Weight	389.4488
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf | https://www.drugbank.ca/drugs/DB00346

Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Alfuzosin is marketed in the United States by Sanofi Aventis under the brand name Uroxatral. UROXATRAL (alfuzosin HCl extended-release tablets) is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. UROXATRAL is not indicated for the treatment of hypertension. Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking agent that exhibits selectivity for alpha(1)-adrenergic receptors in the lower urinary tract. Inhibition of these adrenoreceptors leads to the relaxation of smooth muscle in the bladder neck and prostate, resulting in the improvement in urine flow and a reduction in symptoms in benign prostate hyperplasia. Alfuzosin also inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9135028 \| https://www.ncbi.nlm.nih.gov/pubmed/10812954	Antagonist 2778	8.0 null [pKi]
Alpha-1b adrenergic receptor 44 Target ID: CHEMBL232 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9135028 \| https://www.ncbi.nlm.nih.gov/pubmed/10812954	Antagonist 2778	8.0 null [pKi]
Alpha-1d adrenergic receptor 36 Target ID: CHEMBL223 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/9135028 \| https://www.ncbi.nlm.nih.gov/pubmed/10812954	Antagonist 2778	8.5 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Benign prostatic hyperplasia 28 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf	Primary		Approved 8429	UROXATRAL Approved Use UROXATRAL is indicated for the treatment of signs and symptoms of benign prostatic hyperplasia. UROXATRAL is an alpha adrenergic antagonist, indicated for the treatment of signs and symptoms of benign prostatic hyperplasia. (1) Important Limitations of Use: UROXATRAL is not indicated for treatment of hypertension. (1.1) UROXATRAL is not indicated for use in the pediatric population. (1.1, 8.4, 12.3) 1.1 Important Limitations of Use UROXATRAL is not indicated for the treatment of hypertension. UROXATRAL is not indicated for use in the pediatric population. Launch Date 1.05537602E12

C_max

Value	Dose	Co-administered	Analyte	Population
13.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021287s013lbl.pdf	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALFUZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
194 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021287s013lbl.pdf	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALFUZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021287s013lbl.pdf	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALFUZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
14% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021287s013lbl.pdf	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALFUZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
40 mg 1 times / day single, oral Highest studied dose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_Medr_P3.pdf	healthy, mean age 27 years n = 45 Health Status: healthy Age Group: mean age 27 years Sex: M Population Size: 45 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_Medr_P3.pdf	Other AEs: Dizziness, Headache... Other AEs: Dizziness (8.9%) Headache (6.7%) Malaise (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_Medr_P3.pdf
4.4 mg 2 times / day multiple, oral (mean) Recommended Dose: 4.4 mg, 2 times / day Route: oral Route: multiple Dose: 4.4 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15049986/	unhealthy, mean age 62.6 years n = 93 Health Status: unhealthy Condition: benign prostatic hypertrophy Age Group: mean age 62.6 years Sex: M Population Size: 93 Sources: https://pubmed.ncbi.nlm.nih.gov/15049986/	Disc. AE: Abdominal pain, Diarrhoea... AEs leading to discontinuation/dose reduction: Abdominal pain (grade 1-2, 1.1%) Diarrhoea (grade 1-2, 1.1%) Dizziness (grade 1-2, 3.2%) Headache (grade 1-2, 1.1%) Ventricular fibrillation (grade 1-2, 1.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/15049986/
2.5 mg 3 times / day multiple, oral Recommended Dose: 2.5 mg, 3 times / day Route: oral Route: multiple Dose: 2.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8821687/	unhealthy, mean age 66.9 years n = 13389 Health Status: unhealthy Condition: benign prostatic hypertrophy Age Group: mean age 66.9 years Sex: M Population Size: 13389 Sources: https://pubmed.ncbi.nlm.nih.gov/8821687/	Disc. AE: Vertigo, Syncope... AEs leading to discontinuation/dose reduction: Vertigo (1.35%) Syncope (0.55%) Postural hypotension (0.42%) Headache (0.39%) Nausea (0.46%) Abdominal pain (0.35%) Diarrhoea (0.16%) CNS disorder (NOS) (0.14%) Asthenia (0.19%) Sources: https://pubmed.ncbi.nlm.nih.gov/8821687/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP2A6 707 CYP1A2 1524	CYP1A2 1054	CYP1A 56 CYP2A6 79

Drug as perpetrator

Target	Modality	Activity
CYP1A 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	major		yes (co-administration study) Comment: administration with ketoconazole increased alfuzosin Cmax and AUClast by, 2.3-fold and 3.2 fold, respectively; administration with diltiazem increased Cmax and AUC0-24 of alfuzosin 1.5-fold and 1.3-fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_Pharmr_P1.pdf#page=27 Page: 27,28

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51141	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51141
ChemicalBook	CB4332422	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4332422
MolPort	MolPort-003-666-623	https://www.molport.com/shop/molecule-link/MolPort-003-666-623
eMolecules	901348	https://www.emolecules.com/cgi-bin/more?vid=901348

PubMed

Title	Date	PubMed
alpha-Blockade improves symptoms suggestive of bladder outlet obstruction but fails to relieve it.	2001 Jan	11125359
[Effectiveness of various alfuzosin schedules in patients with benign prostatic hyperplasia (BPH)].	2001 Jan-Feb	11233234
The efficacy and safety of a new once-a-day formulation of an alpha-blocker.	2001 Mar	11306897
Do alpha-blockers prevent the occurrence of acute urinary retention?	2001 Mar	11306896
Does acute urinary retention respond to alpha-blockers alone?	2001 Mar	11306895
Postvoid residual urine in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: pooled analysis of eleven controlled studies with alfuzosin.	2001 Mar	11248620
Alfuzosin: a clinically uroselective alpha1-blocker.	2002 Apr	12022709
Alfuzosin, an alpha1-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia: once daily versus 3 times daily dosing in healthy subjects.	2002 Jul	12139205
alpha-Adrenoceptor antagonists in the treatment of benign prostate hyperplasia.	2002 Jul	12037374
Gateways to clinical trials.	2002 Oct	12500432
First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia.	2003 Nov	14624914
Alfuzosin (uroxatral)--another alpha1-blocker for benign prostatic hyperplasia.	2004 Jan 5	14691408
[Can selective alpha-blockers help the spontaneous passage of the stones located in the uretero-bladder junction?].	2004 Jan-Mar	15688769
New drugs of 2003.	2004 Mar-Apr	15098851
New drugs 04. Part III.	2004 Sep	15382384
Alfuzosin-induced acute hepatitis in a patient with chronic liver disease.	2004 Sep	15280514
Clinical assessment of drug-induced QT prolongation in association with heart rate changes.	2005 Apr	15903123

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Benign Prostatic Hyperplasia Extended-release tablet: 10 mg orally once a day immediately after the same meal each day

Route of Administration: Oral

In Vitro Use Guide

In organ baths, isolated prostatic strips and isolated bladder strips were incubated with vehicle, tadalafil (10⁻⁶ M and 10⁻⁵ M), alfuzosin (3×10⁻⁸ M or 10⁻⁶ M and 10⁻⁵ M) or a combination. Concentration-response curves (CRCs) to norepinephrine were generated on prostatic strips and detrusor strips precontracted with carbachol. Strips were also submitted to electrical field stimulation (EFS). When alfuzosin and tadalafil were combined, the maximal relaxation to norepinephrine on carbachol-precontracted detrusor strips was significantly increased compared with tadalafil alone, and EFS-induced detrusor contractions were better inhibited compared with each compound alone. Tadalafil significantly inhibited norepinephrine-induced prostatic strip contractions by reducing the maximal effect, whereas alfuzosin shifted the CRC of norepinephrine to the right. Combining both tadalafil and alfuzosin resulted in a greater relaxant effect.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:42:59 UTC 2023` Edited by `admin` on `Sat Dec 16 05:42:59 UTC 2023`
Record UNII	75046A1XTN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALFUZOSIN HYDROCHLORIDE

Official Name

English

ALFUZOSIN HYDROCHLORIDE [JAN]

Common Name

English

ALFUZOSIN HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

SL-77499-10

Code

English

ALFUZOSIN HYDROCHLORIDE [USAN]

Common Name

English

ALFUZOSIN HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

ALFUZOSIN HYDROCHLORIDE [MART.]

Common Name

English

ALFUZOSIN HYDROCHLORIDE [MI]

Common Name

English

UROXATRAL

Brand Name

English

ALFUZOSIN HCL

Common Name

English

SL 77 499-10

Code

English

ALFUZOSIN HYDROCHLORIDE [USP-RS]

Common Name

English

ALFUZOSIN HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

Alfuzosin hydrochloride [WHO-DD]

Common Name

English

SL-77-499-10

Code

English

2-FURANCARBOXAMIDE, (±)-N-(3-((4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)METHYLAMINO)PROPYL)TETRAHYDRO-, MONOHYDROCHLORIDE

Common Name

English

(±)-N-(3-((4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)METHYLAMINO)PROPYL)TETRAHYDRO-2-FURAMIDE MONOHYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713