The Comparative Effects of PDE5 Inhibitors (Zaprinast, Sildenafil and Vardenafil) according to the Route of Administration in the Rabbit Model

Moon, Il; Choi, Seong

Abstract

Purpose
Intracavernosal (IC) PDE5 (phosphodiesterase type 5) inhibitors, at tissue levels approaching millimolar concentrations, have been reported to cause penile erection in the absence of sexual stimulation. The objectives of this study were to confirm the effects of three PDE5 inhibitors on penile erection as IC agents, without PNS (pelvic nerve stimulation), and compare the efficacy of these agents on penile erection after intravenous (IV) administration with PNS to that of IC administration without PNS.
Materials and Methods
Anesthetized male New Zealand White rabbits (3.5-4.0kg) were divided into two groups, and the penile hemodynamics was assessed by monitoring of the intracavernosal pressure (ICP) after penile erection induced by PNS (2.5Hz, 10V, 0.8msec for 30 seconds) with the IV administration of 3 PDE5 inhibitors or IC administration without PNS. ICP recordings were normalized to the systemic systolic arterial pressure (SAP). The intracavernosally or intravenously administered doses of zaprinast, sildenafil and vardenafil were 30-1,000mug/kg, 1-30mug/kg and 1-30mug/kg, respectively.
Results
PNS with IV administration of 3 PDE5 inhibitors caused significant frequency-dependent increases in the ICP. The IC administration of zaprinast, sildenafil and vardenafil produced significant increases in the ICP, in dose dependent fashions. The ICP/SAPs with highest doses of zaprinast, sildenafil and vardenafil tested were 0.656, 0.550 and 0.654 in group with IV administration and 0.625, 0.609 and 0.666 in group with IC administration without PNS, respectively.
Conclusions
All 3 PDE5 inhibitors showed increases in the ICP/SAP, in dose dependent manners, in response to IC administration in the absence of PNS as well as PNS with IV administration. IC administration was a much more effective route for penile erection than IV administration.