化合物信息

Drug Groups

approved; investigational

Description

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.

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.

Pharmacology

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.

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

Biotransformation

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.

Absorption

The absolute bioavailability of alprostadil has not been determined.

Half Life

5 to 10 minutes (after a single dose), in healthy adults and neonates.

Protein Binding

Bound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound).

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.

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