ALFUZOSIN

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H27N5O4
Molecular Weight	389.4495
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CCCN=C(C1CCCO1)O)c2nc3cc(c(cc3c(=N)[nH]2)OC)OC

InChI

InChIKey=WNMJYKCGWZFFKR-UHFFFAOYSA-N

InChI=1S/C19H27N5O4/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)

HIDE SMILES / InChI

Molecular Formula	C19H27N5O4
Molecular Weight	389.4495
Charge	0
Count

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

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 64 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 2575	8.0 null [pKi]
Alpha-1b adrenergic receptor 42 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 2575	8.0 null [pKi]
Alpha-1d adrenergic receptor 34 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 2575	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 8043	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 1601 inhibitor 1467 inducer 707		inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1325 CYP2A6 627 CYP1A2 1383	CYP1A2 972	CYP1A 48 CYP2A6 77

Drug as perpetrator

Target	Modality	Activity
CYP1A 110	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2A6 659	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP2A6 659	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP3A4 1772	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP3A4 1772	inhibitor 3045 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 1601	substrate 3113 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 972	substrate 3113 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 1507	inhibitor 1489 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
Clinical significance of alpha1-adrenoceptor selectivity in the management of benign prostatic hyperplasia.	2001	12230262
Initial choices and final outcomes in lower urinary tract symptoms.	2001	11786676
Long-term aspects of medical treatment of BPH.	2001	11786671
Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia.	2001	11583366
alpha-Blockade improves symptoms suggestive of bladder outlet obstruction but fails to relieve it.	2001 Jan	11125359
[Dalphaz-retard treatment of urination disorders in men and women].	2001 Jul-Aug	11569237
[Long-term therapy of benign prostatic hyperplasia. Our experience].	2001 Mar	11346714
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
Worldwide experience with alfuzosin and tamsulosin.	2001 Oct	11597528
Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms.	2002	11950378
Alfuzosin: a clinically uroselective alpha1-blocker.	2002 Apr	12022709
Long-term risk of re-treatment of patients using alpha-blockers for lower urinary tract symptoms.	2002 Apr	11912399
Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials.	2002 Dec 12	12477383
Long-term safety and efficacy of a once-daily formulation of alfuzosin 10 mg in patients with symptomatic benign prostatic hyperplasia: open-label extension study.	2002 Jan	11999466
[Comparative evaluation of the effectiveness and safety of combined drug therapy of patients with benign prostatic hyperplasia with finasteride and alfuzozine].	2002 Jan-Feb	11877966
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
Alfuzosin in the treatment of high leak-point pressure in children with neurogenic bladder.	2002 Nov	12410754
[Drug therapy of benign prostatic hyperplasia syndrome with alpha 1-receptor blockers. Basic principles and clinical results].	2002 Sep	12426859
Safety and efficacy of alfuzosin 10 mg once-daily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies.	2003 Aug	12887479
Use of alpha-blockers and the risk of hip/femur fractures.	2003 Dec	14641795
Prostatic tissual distribution of alfuzosin in patients with benign prostatic hyperplasia following repeated oral administration.	2003 Jul	12814682
Comparison of the relaxant effects of alfuzosin, phentolamine and sildenafil on rabbit isolated corpus cavernosum.	2003 Jun	12780851
Selective, sensitive and rapid liquid chromatography-tandem mass spectrometry method for the determination of alfuzosin in human plasma.	2003 May 25	12705976
First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia.	2003 Nov	14624914
Alfuzosin for the management of benign prostate hyperplasia.	2003 Nov	14596659
Alfuzosin treatment for chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized, double-blind, placebo-controlled, pilot study.	2003 Sep	12946740
[Pharmacologic treatment of benign prostatic hyperplasia].	2003 Sep 14	14596018
A comparison of four different alpha1-blockers in benign prostatic hyperplasia patients with and without diabetes.	2004	15764250
Priapism as a possible acute side effect of radical radiotherapy for prostate cancer.	2004 Apr	15182410
Comparative efficacy of two alpha-adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargement.	2004 Apr	15049986
Ejaculatory dysfunction and alpha-adrenoceptor antagonists.	2004 Aug	15291886
Real life practice in the management of benign prostatic hyperplasia.	2004 Jan	15091049
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
[A suggested treatment algorithm in nocturnal enuresis with emphasis on partial responders].	2004 Jul	15138691
Alfuzosin once daily facilitates return to voiding in patients in acute urinary retention.	2004 Jun	15126812
Patients with bladder outlet obstruction who refuse treatment show no clinical and urodynamic change after long-term follow-up.	2004 Mar	15185815
Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia.	2004 Mar	14767264
New drugs of 2003.	2004 Mar-Apr	15098851
Prostate size influences the outcome after presenting with acute urinary retention.	2004 Sep	15329112
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
Early symptom improvement of benign prostatic hyperplasia (BPH) treated with once daily alfuzosin.	2005 Aug	16197598
Symptom deterioration during treatment and history of AUR are the strongest predictors for AUR and BPH-related surgery in men with LUTS treated with alfuzosin 10 mg once daily.	2005 Aug	16098361
A pharmacoepidemiological approach to investigating inappropriate physician prescribing in a managed care setting in Israel.	2005 Feb	15726856
[The role of alpha1-adrenoblocker alfuzosine in diagnostic-therapeutic algorithm of hyperactive urinary bladder management in women and selection of patients for treatment with M-cholinergic antagonists].	2005 Jan-Feb	15776831
Re: Alfuzosin once daily facilitates return to voiding in patients in acute urinary retention.	2005 Jul	15947706
Efficacy and safety of two doses (10 and 15 mg) of alfuzosin or tamsulosin (0.4 mg) once daily for treating symptomatic benign prostatic hyperplasia.	2005 May	15839922

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 `Fri Jun 25 21:51:53 UTC 2021` Edited by `admin` on `Fri Jun 25 21:51:53 UTC 2021`
Record UNII	90347YTW5F
Record Status	`Validated (UNII)`
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Name

Type

Language

ALFUZOSIN

Official Name

English

ALFUZOSIN [VANDF]

Common Name

English

XATRAL

Brand Name

English

ALFUZOSIN [HSDB]

Common Name

English

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

Systematic Name

English

ALFUZOSIN [INN]

Common Name

English

ALFUZOSIN [MI]

Common Name

English

ALFUZOSIN [WHO-DD]

Common Name

English

(+/-)-N-(3-((4-AMINO-6,7-DIMETHOXYQUINAZOLIN-2-YL)(METHYL)AMINO)PROPYL)TETRAHYDROFURAN-2-CARBOXAMIDE

Systematic Name

English

NSC-760065

Code

English

Classification Tree Code System Code

WHO-ATC

G04CA51