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Identification
NameAlfuzosin
Accession NumberDB00346  (APRD00490)
Typesmall molecule
Groupsapproved, investigational
Description

Alfuzosin (INN, provided as the hydrochloride salt) is an alpha-adrenergic blocker used to treat benign prostatic hyperplasia (BPH). It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(±)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furamide Not AvailableWHO
AlfuzosinNot AvailableBAN
AlfuzosinaNot AvailableDCIT
AlfuzosineFrenchDCF
AlfuzosinumLatinINN
N-[3-[(4-amino-6,7-dimethoxy-quinazolin-2-yl)- methyl-amino]propyl] tetrahydrofuran- 2-carboxamideNot AvailableIUPAC
Salts
Name/CAS Structure Properties
Alfuzosin Hydrochloride
Thumb Not applicable DBSALT001063
Brand names
NameCompany
AlcininPharmathen
Alfasin XRIncepta
AlfetimSanofi-Aventis
AlfooDr. Reddy's
AlfuRowex
AlfuranTerapia
AlfusozinaGrey Inversiones
FlotralRanbaxy
FualAlkem
ProfuzoNeiss
RantralRanbaxy
UritenSquare
UroxatralSanofi-Aventis
XantralSanofi-Aventis
XatralSanofi-Aventis
XelfloSun
ZatralEskayef
Brand mixtures
Brand NameIngredients
DutalfaAlfuzosin and Dutasteride
Categories
CAS number81403-80-7
WeightAverage: 389.4488
Monoisotopic: 389.206304377
Chemical FormulaC19H27N5O4
InChI KeyWNMJYKCGWZFFKR-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}oxolane-2-carboxamide
SMILES
COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N(C)CCCNC(=O)C1CCCO1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassNaphthyridines
SubclassQuinazolines
Direct parentQuinazolinamines
Alternative parentsAnisoles; Alkyl Aryl Ethers; Aminopyrimidines and Derivatives; Primary Aromatic Amines; Oxolanes; Tetrahydrofurans; Tertiary Amines; Secondary Carboxylic Acid Amides; Carboxylic Acids; Enolates; Polyamines
Substituentsphenol ether; anisole; alkyl aryl ether; aminopyrimidine; pyrimidine; benzene; primary aromatic amine; tetrahydrofuran; oxolane; carboxamide group; secondary carboxylic acid amide; tertiary amine; ether; carboxylic acid derivative; polyamine; carboxylic acid; enolate; amine; organonitrogen compound; primary amine
Classification descriptionThis compound belongs to the quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
Pharmacology
IndicationFor the reduction of urinary obstruction and relief of associated manifestations (eg. sensation of incomplete bladder emptying or straining, urgency, interrupted or weak stream) in patients with symptomatic beningn prostatic hyperplasia.
PharmacodynamicsAlfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the human prostate, alfuzosin antagonizes phenylephrine (alpha(1) agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1a adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that alfuzosin competitively antagonized the pressor effects of phenylephrine (an alpha(1) agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of alfuzosin results from a decrease in systemic vascular resistance and the parent compound alfuzosin is primarily responsible for the antihypertensive activity.
Mechanism of actionAlfuzosin 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.
AbsorptionAbsorption is 50% lower under fasting conditions
Volume of distribution
  • 3.2 L/kg [healthy male middle-aged volunteers]
Protein binding82%-90%
Metabolism

Hepatic. Alfuzosin undergoes extensive metabolism by the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized by three metabolic pathways: oxidation, O-demethylations, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its metabolism.

Route of eliminationFollowing oral administration of 14C-labeled alfuzosin solution, the recovery of radioactivity after 7 days (expressed as a percentage of the administered dose) was 69% in feces and 24% in urine.
Half life10 hours
ClearanceNot Available
ToxicitySide effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.6215
Caco-2 permeable - 0.5504
P-glycoprotein substrate Substrate 0.8105
P-glycoprotein inhibitor I Inhibitor 0.5971
P-glycoprotein inhibitor II Non-inhibitor 0.5479
Renal organic cation transporter Non-inhibitor 0.7288
CYP450 2C9 substrate Non-substrate 0.8722
CYP450 2D6 substrate Non-substrate 0.7748
CYP450 3A4 substrate Substrate 0.7766
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8017
Ames test Non AMES toxic 0.559
Carcinogenicity Non-carcinogens 0.8721
Biodegradation Not ready biodegradable 0.9945
Rat acute toxicity 2.6826 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8527
hERG inhibition (predictor II) Inhibitor 0.5929
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Uroxatral 10 mg 24 Hour tablet4.06USDtablet
Uroxatral 10 mg tablet3.95USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States61499401997-08-222017-08-22
United States46614911994-01-182011-01-18
Canada22642502005-07-052017-08-22
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
water solubility2.82e-01 g/lALOGPS
logP2.02ALOGPS
logP1.19ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)14.64ChemAxon
pKa (strongest basic)7.3ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count2ChemAxon
polar surface area111.83ChemAxon
rotatable bond count8ChemAxon
refractivity107.11ChemAxon
polarizability42.71ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Mathias Scheer, “Alfuzosin tablets and synthesis.” U.S. Patent US20060062845, issued March 23, 2006.

US20060062845
General Reference
  1. McKeage K, Plosker GL: Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53. Pubmed
  2. Wilde MI, Fitton A, McTavish D: Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs. 1993 Mar;45(3):410-29. Pubmed
  3. Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. Pubmed
  4. Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. Pubmed
  5. Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. Pubmed
External Links
ResourceLink
KEGG DrugD01692
PubChem Compound2092
PubChem Substance46508512
ChemSpider2008
ChEBI51141
ChEMBLCHEMBL709
Therapeutic Targets DatabaseDCL000664
PharmGKBPA164774795
Drug Product Database2245565
RxListhttp://www.rxlist.com/cgi/generic/uroxatral.htm
Drugs.comhttp://www.drugs.com/cdi/alfuzosin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/uro1685.shtml
WikipediaAlfuzosin
ATC CodesG04CA01
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelshow(72.9 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
BoceprevirBoceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Concomitant use of alfuzosin with a strong CYP3A4 inhibitor is a listed contraindication according to alfuzosin prescribing information.
ItraconazoleThe antifungal increases the effect of alfuzosin
KetoconazoleThe antifungal increases the effect of alfuzosin
RitonavirRitonavir increases the effect/toxicity of alfuzosin
TadalafilTadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
TamsulosinConcomitant use of alpha1-adrenergic antagonists, Tamsulosin and Alfuzosin, may result in additive antihypertensive effects. Combination therapy is not recommended.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
TelithromycinTelithromycin may reduce clearance of Alfuzosin. Consider alternate therapy.
TerazosinAdditive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy should be avoided.
VardenafilAdditive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Alfuzosin, may occur. Monitor for hypotension during concomitant therapy.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of alfuzosin by decreasing its metabolism. Use of alfuzosin with strong CYP3A4 inhibitors is contraindicated by the manufacturer.
Food Interactions
  • Take after a meal (always the same meal), product bioavailability is reduced when taken on an empty stomach.

Targets

1. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kenny BA, Miller AM, Williamson IJ, O’Connell J, Chalmers DH, Naylor AM: Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Br J Pharmacol. 1996 Jun;118(4):871-8. Pubmed
  3. Lee M: Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia. Am J Health Syst Pharm. 2003 Jul 15;60(14):1426-39. Pubmed
  4. Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. Pubmed
  5. Lowe FC: Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms. Clin Ther. 2004 Nov;26(11):1701-13. Pubmed
  6. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. Pubmed
  7. Faure C, Pimoule C, Vallancien G, Langer SZ, Graham D: Identification of alpha 1-adrenoceptor subtypes present in the human prostate. Life Sci. 1994;54(21):1595-605. Pubmed
  8. Beique L, Por CP, Evans MF: Are the new selective alpha-blockers better than non-selective alpha-blockers for benign prostatic hyperplasia? Can Fam Physician. 1998 Dec;44:2659-62. Pubmed
  9. McVary KT: BPH: epidemiology and comorbidities. Am J Manag Care. 2006 Apr;12(5 Suppl):S122-8. Pubmed
  10. Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. Pubmed
  11. Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. Pubmed

2. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kenny BA, Miller AM, Williamson IJ, O’Connell J, Chalmers DH, Naylor AM: Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Br J Pharmacol. 1996 Jun;118(4):871-8. Pubmed
  3. Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. Pubmed
  4. Lowe FC: Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms. Clin Ther. 2004 Nov;26(11):1701-13. Pubmed
  5. Faure C, Pimoule C, Vallancien G, Langer SZ, Graham D: Identification of alpha 1-adrenoceptor subtypes present in the human prostate. Life Sci. 1994;54(21):1595-605. Pubmed
  6. Beique L, Por CP, Evans MF: Are the new selective alpha-blockers better than non-selective alpha-blockers for benign prostatic hyperplasia? Can Fam Physician. 1998 Dec;44:2659-62. Pubmed
  7. McVary KT: BPH: epidemiology and comorbidities. Am J Manag Care. 2006 Apr;12(5 Suppl):S122-8. Pubmed
  8. Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. Pubmed
  9. Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. Pubmed

3. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kenny BA, Miller AM, Williamson IJ, O’Connell J, Chalmers DH, Naylor AM: Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Br J Pharmacol. 1996 Jun;118(4):871-8. Pubmed
  3. Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15. Pubmed
  4. Lowe FC: Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms. Clin Ther. 2004 Nov;26(11):1701-13. Pubmed
  5. Faure C, Pimoule C, Vallancien G, Langer SZ, Graham D: Identification of alpha 1-adrenoceptor subtypes present in the human prostate. Life Sci. 1994;54(21):1595-605. Pubmed
  6. McVary KT: BPH: epidemiology and comorbidities. Am J Manag Care. 2006 Apr;12(5 Suppl):S122-8. Pubmed
  7. Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96. Pubmed
  8. Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4. Pubmed

4. Potassium voltage-gated channel subfamily H member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 2 Q12809 Details

References:

  1. The hERG Cardiac Potassium Channel: Structure, Function and Long QT Syndrome … ( By Novartis Foundation) books.google.ca/books?isbn=0470021411

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Guay DR: Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor antagonist for symptomatic benign prostatic hyperplasia. Am J Geriatr Pharmacother. 2004 Mar;2(1):14-23. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on March 19, 2014 13:54