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Identification
Name Alfuzosin
Accession Number DB00346 (APRD00490)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Alfusosine
Salts Not Available
Brand names
Name Company
Uroxatral
Xatral
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic alpha-Antagonists
CAS number 81403-80-7
Weight Average: 389.4488
Monoisotopic: 389.206304377
Chemical Formula C19H27N5O4
InChI Key InChIKey=WNMJYKCGWZFFKR-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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Quinazolines
Substructures
  • Quinazolines
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Furans
  • Cyanamides
  • Phenyl Esters
Pharmacology
Indication For 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.
Pharmacodynamics Alfuzosin 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 action 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.
Absorption Absorption is 50% lower under fasting conditions
Volume of distribution
  • 3.2 L/kg [healthy male middle-aged volunteers]
Protein binding 82%-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 elimination Following 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 life 10 hours
Clearance Not Available
Toxicity Side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet, extended release Oral
Prices
Unit description Cost Unit
Uroxatral 10 mg 24 Hour tablet 4.06 USD tablet
Uroxatral 10 mg tablet 3.95 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6149940 1997-08-22 2017-08-22
United States 4661491 1994-01-18 2011-01-18
Canada 2264250 2005-07-05 2017-08-22
Properties
State solid
Experimental Properties
Property Value Source
logP 1.4 Not Available
Predicted Properties
Property Value Source
water solubility 2.82e-01 g/l ALOGPS
logP 2.02 ALOGPS
logP 1.19 ChemAxon
logS -3.1 ALOGPS
pKa (strongest acidic) 14.64 ChemAxon
pKa (strongest basic) 7.3 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 111.83 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 107.11 ChemAxon
polarizability 42.71 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D01692 Link_out
PubChem Compound 2092 Link_out
PubChem Substance 46508512 Link_out
ChemSpider 2008 Link_out
ChEBI 51141 Link_out
ChEMBL 51141 Link_out
Therapeutic Targets Database DCL000664 Link_out
PharmGKB PA164774795 Link_out
Drug Product Database 2245565 Link_out
RxList http://www.rxlist.com/cgi/generic/uroxatral.htm Link_out
Drugs.com http://www.drugs.com/cdi/alfuzosin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/uro1685.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Alfuzosin Link_out
ATC Codes
  • G04CA01
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (72.9 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Conivaptan CYP3A4 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.
Itraconazole The antifungal increases the effect of alfuzosin
Ketoconazole The antifungal increases the effect of alfuzosin
Ritonavir Ritonavir increases the effect/toxicity of alfuzosin
Tadalafil Tadalafil may enhance the hypotensive effect of Alfusozin. Monitor for hypotension during concomitant therapy.
Tamsulosin Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Alfuzosin, may result in additive antihypertensive effects. Combination therapy is not recommended.
Telithromycin Telithromycin may reduce clearance of Alfuzosin. Consider alternate therapy.
Terazosin Additive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy should be avoided.
Vardenafil Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Alfuzosin, may occur. Monitor for hypotension during concomitant therapy.
Voriconazole Voriconazole, 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

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out
Gene: ADRA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19