Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction.

Abstract

Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the diameter of cavernous arteries; this leads to erection. Following intracavernous administration, alprostadil is either locally metabolised or rapidly cleared from the penis into the systemic circulation where it is extensively metabolised by the lungs. Studies suggest that long term use of intracavernous alprostadil may increase penile blood flow, although the clinical relevance of this is not currently known. In men with erectile dysfunction (ED), short term trials have shown that intracavernous alprostadil is superior or equal, in inducing erections, to other intracavernous agents such as papaverine, the combination of papaverine plus phentolamine, linsidomine and topical nitroglycerin (glyceryl trinitrate). Intracavernous alprostadil induced erections in around 70% of patients with ED of various origins in short term studies. 49 to 84% of patients accept the offer of joining self-injection programmes and 13 to 60% of these patients withdraw from such programmes for a variety of reasons. At therapeutic doses, intracavernous alprostadil is well tolerated. The most common adverse event of transient penile pain occurred in around one-third of patients and in 11% of injections, causing 3 to 5% of patients to withdraw from self-injection programmes. Potentially serious adverse events such as priapism and fibrosis occurred in 4 and 8% of patients. Overall, available data suggest that the efficacy of intracavernous alprostadil is superior or equal to that of other erectogenic agents which are in use. Furthermore, the drug is well tolerated especially with regard to serious adverse events. Thus, although further research is necessary to confirm its use in combination with other agents, alprostadil appears likely to become the intracavernous agent of choice for the management of erectile dysfunction.