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 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 2737	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 2737	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 2737	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 8307	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 1670 inhibitor 1532 inducer 753		inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1410 CYP2A6 670 CYP1A2 1463	CYP1A2 1013	CYP1A 55 CYP2A6 79

Drug as perpetrator

Target	Modality	Activity
CYP1A 119	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2A6 702	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-287_Uroxatral_BioPharmr_P1.pdf#page=34 Page: 34.0	no
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21287_uroxatral_lbl.pdf#page=5 Page: 5.0	no
CYP3A4 1857	inhibitor 3185 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 1670	substrate 3264 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 1013	substrate 3264 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 1603	inhibitor 1584 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
Initial choices and final outcomes in lower urinary tract symptoms.	2001	11786676
Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia.	2001	11583366
Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker.	2001 Dec	11750253
Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial.	2001 Dec	11744466
A quantitative analysis of antagonism and inverse agonism at wild-type and constitutively active hamster alpha1B-adrenoceptors.	2001 Jan	11191834
[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
Does acute urinary retention respond to alpha-blockers alone?	2001 Mar	11306895
Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia.	2002	11893233
Tamsulosin: an update of its role in the management of lower urinary tract symptoms.	2002	11790159
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
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
Gateways to clinical trials.	2002 Oct	12500432
Randomised, placebo controlled, double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention.	2002 Oct	12361896
Use of alpha-blockers and the risk of hip/femur fractures.	2003 Dec	14641795
Benign prostatic hyperplasia.	2003 Feb	12619342
The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction.	2003 Feb	12544303
Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia.	2003 Jul 15	12892027
Proceedings of the 99th meeting of the Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee. May 29th and 30th, 2003.	2003 Jun 17	12814989
Estimated costs of treatment of benign prostate hyperplasia in Brazil.	2003 May-Jun	15745527
Alfuzosin for the management of benign prostate hyperplasia.	2003 Nov	14596659
A comparison of four different alpha1-blockers in benign prostatic hyperplasia patients with and without diabetes.	2004	15764250
Drug approval highlights for 2003.	2004 Feb	14872168
Alfuzosin improves penile erection triggered by apomorphine in spontaneous hypertensive rats.	2004 Jan	14667526
[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
On call. My doctor gave me a prescription for Uroxatral to treat my enlarged prostate. I tried to look up this medicine in your Harvard Medical School Guide to Men's Health, but I couldn't find it. What can you tell me about Uroxatral?	2004 Jun	15210419
Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor antagonist for symptomatic benign prostatic hyperplasia.	2004 Mar	15555475
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
Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms.	2004 Nov	15639685
Delayed complications of discontinuation of intrathecal baclofen therapy: resurgence of dyssynergic voiding, which triggered off autonomic dysreflexia and hydronephrosis.	2004 Oct	15224085
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
Early symptom improvement of benign prostatic hyperplasia (BPH) treated with once daily alfuzosin.	2005 Aug	16197598
Alfuzosin 10 mg once daily in the management of acute urinary retention: results of a double-blind placebo-controlled study.	2005 Jan	15667868
[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
Lower urinary tract symptoms suggestive of benign prostatic hyperplasia: latest update on alpha-adrenoceptor antagonists.	2005 Jun	15871733
The vasodilatory effect of alfuzosin and tamsulosin in passive orthostasis: a randomised, double-blind, placebo-controlled study.	2005 Mar	15716198
The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia.	2005 Mar	15705083
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
Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction.	2005 Nov	16217354
Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects.	2005 Oct	16230138
A comparative study on the safety and efficacy of tamsulosin and alfuzosin in the management of symptomatic benign prostatic hyperplasia: a randomized controlled clinical trial.	2005 Sep-Oct	16222890

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 17 18:46:52 UTC 2022` Edited by `admin` on `Sat Dec 17 18:46:52 UTC 2022`
Record UNII	75046A1XTN
Record Status	`Validated (UNII)`
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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