Alprostadil (PGE₁) is one of the prostaglandins, a family of naturally occurring acidic lipids with various pharmacological effects. Endogenous PGE₁ is derived from dihomo-gamma-linolenic acid, a fatty acid found within the phospholipids of cellular membranes. As an endogenous substance, PGE₁ exerts its biological effects either directly or indirectly by regulating and modifying the synthesis and effects of other hormones and mediators.

Mode of Action Alprostadil is a smooth muscle relaxant. Precontracted isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery are relaxed by alprostadil. Alprostadil has been shown to bind to specific receptors in human penile tissue. Two types of receptors that differ in their PGE₁ binding affinity have been identified. The binding of alprostadil to its receptors is accompanied by an increase in intracellular cAMP levels. Human cavernous smooth muscle cells respond to alprostadil by releasing intracellular calcium into the surrounding medium. Smooth muscle relaxation is associated with a reduction of the cytoplasmic free calcium concentration. Alprostadil also attenuates presynaptic noradrenaline release in the corpus cavernosum which is essential for the maintenance of a flaccid and non-erect penis.

Alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernous arteries. This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism.

Alpha-Cyclodextrin

After reconstitution, PGE₁ immediately dissociates from the a-cyclodextrin inclusion complex; the in vivo disposition of both components occurs independently after administration. After intravenous infusion of radiolabeled a-cyclodextrin to healthy volunteers, the radiolabeled components were rapidly eliminated within 24-hours, urine accounting for 81-83% of radioactivity and feces for 0.1%. There was no evidence of significant accumulation of radiolabeled a-cyclodextrin in the body even after 7 days of repeated intravenous injection. After intracavernous administration in monkeys, radiolabeled a-cyclodextrin was rapidly distributed from the injection site with less than 0.1% of the dose remaining in the penis 1 hour after administration. There was no evidence of tissue retention of radiolabeled a-cyclodextrin in monkeys.

Alprostadil Absorption: After intracavernous injection of 20 mcg of edex^Ã? in 24 patients with erectile dysfunction, mean systemic plasma concentrations of PGE₁ increased from baseline of 0.8 ± 0.6 pg/mL to a peak (C_max) of 16.8 ± 18.9 pg/mL (corrected for baseline) within 2 to 5 minutes and dropped to endogenous plasma levels within 2 hours (Table 1). The absolute bioavailability of alprostadil estimated from systemic exposure was about 98% as compared to the same dose given by a short-term intravenous infusion.

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