アルプロスタジル 化学特性,用途語,生産方法
効能
血管拡張薬, プロスタグランジンE1受容体作動薬
商品名
パルクス (大正製薬); パルクス (大正製薬); リプル (田辺三菱製薬); リプル (田辺三菱製薬)
説明
Prostaglandin E1 is an endogenous prostaglandin with vasodilatory, anti-platelet, and anti-hypertensive activities. It is in clinical use for the treatment of erectile dysfunction and the emergency management of infants with patent ductus arteriosus. It has also been used in the treatment of peripheral arterial occlusive disease (PAD).
化学的特性
Crystalline Solid
使用
A primary Prostaglandin; easily crystallized from purified biological extracts. Vasodilator (peripheral)
適応症
Alprostadil (prostaglandin E
1 [PGE
1]; Edex, Topiglan)
exerts a number of effects, including systemic vasodilation,
inhibition of platelet aggregation, and stimulation
of intestinal motility. PGE
1 relaxes isolated smooth
muscle cells contracted by norepinephrine. It has become
widely used in the treatment of ED. Alprostadil
binds with PGE receptors and results in a cyclic adenosine
monophosphate (cAMP) mediated smooth muscle
relaxation. Little is known about the pharmacokinetics
of PGE
1, but it is believed that as much as 80% is metabolized
in one pass through the lungs. Such rapid
degradation probably accounts for its lack of significant
cardiovascular side effects when administered intracavernosally.
PGE
1 can also be metabolized in the penis.
世界保健機関（WHO）
Alprostadil, a prostaglandin with vasodilating and platelet antiaggregatory
activity, was introduced in 1984 for the treatment of chronic arterial
obstruction. Intravenous administration of the drug has been associated with
adverse effects that have sometimes been severe. These include allergic reactions,
pulmonary oedema and cardiac insufficiency. Interactions with antihypertensive
agents, vasodilators, anticoagulants and inhibitors of platelet aggregation have
also occurred. This has led the German agency to modify the approved product
information of alprostadil preparations to warn against these adverse effects.
生物学の機能
Prostaglandin E1 is produced endogenously to relax vascular smooth muscle and cause vasodilation by activating the adenylate cyclase/cAMP pathway. Recent studies show that the cAMP is important in the PGE1 relaxation of penile erectile tissue and vasodilation of penile resistance arteries. Moreover, agents that stimulate the release of cAMP also crossactivate the NO/cGMP cascade.
一般的な説明
PGE1, Alprostadil (Prostin VR Pediatric), is a naturally occurring prostaglandin that has found particular use in maintaining a patent (opened) ductus arteriosus in infants with congenital defects that restrict pulmonary or systemic blood flow.
Alprostadil must be administered intravenously continually at a rate of approximately 0.1 μg/kg/min to maintain the patency of the ductus arteriosus until corrective surgery can be performed. Up to 80% of circulating alprostadil may be metabolized in a single pass through the lungs. Because apnea has been observed in 10% to 12% of neonates with congenital heart defects, this product should be administered only when ventilatory assistance is immediately available. Other commonly observed side effects include decreased arterial blood pressure, which should be monitored during infusion; inhibited platelet aggregation, which might aggravate bleeding tendencies; and diarrhea.
生物活性
Prostaglandin with some selectivity for EP 3 and EP 4 receptors (K i values are 1.1, 2.1, 36, 10? and 33 nM for mouse EP 3 , EP 4 , EP 1 , EP 2 and IP receptors respectively). Inhibits platelet aggregation and is a vasodilator in vivo .
作用機序
PGE
1 is not orally effective. Its therapeutic success
depends on its being injected intracavernosally or administered
transurethrally or intraurethrally. PGE
1 has
also been used in combination with other agents, such as
papaverine. The injection does not appear to produce
any long-term side effects on penile smooth muscle.
Transurethral therapy with alprostadil, such as MUSE
(alprostadil urethral suppository or medicated urethral
system for erection) is also an effective therapeutic
technique, and there may be a role for this form of administration
in selected patients with ED.The intracavernosal
injection of alprostadil (e.g., alprostadil alfadex;
Edex, Viridal) is safe and effective in patients with ED
when sildenafil is ineffective. Both of these delivery systems
have been used in the treatment of ED. MUSE can
also be used in conjunction with a penile constrictor device
(e.g., ACTIS).
臨床応用
Prostaglandin E1 (PGE1; Alprostadil) is approved for the intracavernosal (Caverject, Edex)or
intraurethral suppository (Muse) treatment of ED. A three-drug combination of PGE1, papaverine,
and phentolamine sometimes is used as an intracavernosal injection to achieve a synergistic action.
Erectile dysfunction that is medication-induced or caused by endocrine problems, such as
hypogonadism or hyper- or hypothyroidism, should be evaluated and appropriately treated before
PGE1 treatment is considered.
代謝
The major route of excretion of PGE1 metabolites is via the kidney. Its elimination half-life is 5 to 10 minutes. If any alprostadil is systemically absorbed, it is metabolized by a single pass through the lungs. The onset of action is within 10 minutes, and the time to peak effect is less than 20 minutes. The duration of action is 1 to 3 hours for the intracavernosal injection and 30 to 60 minutes for the intraurethral suppository.
アルプロスタジル 上流と下流の製品情報
原材料
準備製品