Possible hemodynamic pathways of intraurethral prostaglandin-E1 (MUSE™)

Abstract

Intraurethral application of prostaglandin-E1 (MUSEt) is a well-tolerated pharmacotherapy for erectile dysfunction. However, the physiological mechanisms of drug transfer into the cavernous bodies are not completely clear. Using spongiosography in 35 patients, our study tried to elucidate existing shunt mechanisms. The X-rays show venous drainage through the deep dorsal vein up to the plexus Santorini. The circumflex veins are also contrasted and the cavernous bodies show opacification in their distal portion only. Structures shunting directly between the corpus spongiosum and the cavernous bodies were not demonstrable. Retrograde filling of the cavernous bodies through the deep dorsal vein and its circumflex braches seems to be the most relevant way of drug transfer after intraurethral application of prostaglandin-E1. Diffusion into the cavernous bodies or a systemic mechanism of action does not seem probable.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Vasoactive agents can be administered topically to the urethral mucosa and can apparently be absorbed into the corpus spongiosum and transferred to the CC. Retrograde filling of the cavernosal bodies through the deep dorsal vein and its circumflex branches seems to be the most relevant way of drug transfer after intraurethral application of prostaglandin E 1 (Bschleipfer et al, 2004). PGE 1 (alprostadil) and a PGE 1 /prazosin combination was demonstrated to produce erections in a majority of patients with chronic organic ED (Peterson et al, 1998).…”

Current role of local treatments for erectile dysfunction in the real-life setting

“…Instillation should be performed after micturition to ensure a moist environment for improved dissolution and absorption of the pellet. Alprostadil then diffuses through the venous network connecting the corpus spongiosum to the corpora cavernosa, resulting in smooth muscle cell relaxation of the corpora cavernosa [13]. Overall, erectile function is improved in 59-78% of patients with erectile dysfunction [11,14,15].…”

“…The 500 mg dose has been identified as the minimal concentration for an erectile response in the majority of patients [16]. The large doses of intraurethral alprostadil needed to produce erections in comparison to intracavernosal injections are mandated by the significant amount of drug lost to the systemic circulation through the in-deep dorsal vein and its circumflex branches [13]. Erections are evoked in 5 min, and they are preserved for a time frame ranging from 30 to 60 min.…”

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)

“…In the absence of structural shunts between the corpus spongiosum and CC, the retrograde transfer of PGE 1 might be facilitated through circulation in the deep dorsal vein and its circumflex branches. 292 Therefore, MUSE would require approximately 50 times the IC dose of PGE 1 for the same therapeutic efficiency.…”