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药品详细

Alfuzosin(阿夫唑嗪)

化学结构式图
中文名
阿夫唑嗪
英文名
Alfuzosin
分子式
C19H27N5O4
化学名
N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}oxolane-2-carboxamide
分子量
Average: 389.4488
Monoisotopic: 389.206304377
CAS号
81403-80-7
ATC分类
G04C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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]

生产厂家
  • Sanofi aventis us llc
封装厂家
参考
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
剂型
规格
化合物类型
Type small molecule
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
适应症
药理
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
理化性质
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
药物相互作用
Drug Interaction
Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
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.
Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
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.
食物相互作用
  • Take after a meal (always the same meal), product bioavailability is reduced when taken on an empty stomach.

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