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药品详细

Alprostadil(前列地尔)

化学结构式图
中文名
前列地尔
英文名
Alprostadil
分子式
C20H34O5
化学名
7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid
分子量
Average: 354.481
Monoisotopic: 354.240624198
CAS号
745-65-3
ATC分类
C01E 未知;G04B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Alprostadil is produced endogenously and causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. In infants, it is used for palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. In adults, it is used for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

生产厂家
  • Bedford laboratories div ben venue laboratories inc
  • Pfizer inc
  • Pharmacia and upjohn co
  • Schwarz pharma ag
  • Teva parenteral medicines inc
  • Vivus inc
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Carboxylic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Ketones
适应症
药理
Indication For palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. Also for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.
Pharmacodynamics Alprostadil (prostaglandin E1) is produced endogenously to relax vascular smooth muscle and cause vasodilation. In adult males, the vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arteriolar inflow and expansion of the lacunar spaces within the corpora. As the expanded corporal sinusoids are compressed against the tunica albuginea, venous outflow through the subtunical vessels is impeded and penile rigidity develops. This is referred to as the corporal veno-occlusive mechanism. In infants, the vasodilatory effects of alprostadil increase pulmonary or systemic blood flow.
Mechanism of action Alprostadil causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This is because, as a form of prostaglandinE1 (PGE1) it has multiple effects on blood flow. This results in increased pulmonary or systemic blood flow in infants. In cyanotic congenital heart disease, alprostadil's actions result in an increased oxygen supply to the tissues. In infants with interrupted aortic arch or very severe aortic coarctation, alprostadil maintains distal aortic perfusion by permitting blood flow through the DA from the pulmonary artery to the aorta. In infants with aortic coarctation, alprostadil reduces aortic obstruction either by relaxing ductus tissue in the aortic wall or by increasing effective aortic diameter by dilating the DA. In infants with these aortic arch anomalies, systemic blood flow to the lower body is increased, improving tissue oxygen supply and renal perfusion. When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea.
Absorption The absolute bioavailability of alprostadil has not been determined.
Volume of distribution Not Available
Protein binding Bound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound).
Metabolism
Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by beta- and omega-oxidation.
Route of elimination Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by β- and ω-oxidation. The metabolites are excreted primarily by the kidney, and excretion is essentially complete within 24 hours after administration.
Half life 5 to 10 minutes (after a single dose), in healthy adults and neonates.
Clearance Not Available
Toxicity Oral, mouse: LD50 = 186 mg/kg; Oral, rat: LD50 = 228 mg/kg. Apnea, bradycardia, pyrexia, hypotension, and flushing may be signs of drug overdosage.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 115-116 °C Not Available
water solubility 26.7 mg/L Not Available
logP 3.20 AVDEEF,A ET AL. (1995)
pKa 4.85 (at 25 °C) AVDEEF,A ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 7.88e-02 g/l ALOGPS
logP 3.04 ALOGPS
logP 3.59 ChemAxon
logS -3.6 ALOGPS
pKa (strongest acidic) 4.35 ChemAxon
pKa (strongest basic) -1.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 94.83 ChemAxon
rotatable bond count 13 ChemAxon
refractivity 98.32 ChemAxon
polarizability 41.88 ChemAxon
药物相互作用
食物相互作用
Not Available

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