Comparison of Efficacy and Time of Onset between Vardenafil and Sildenafil in Facilitating Pelvic Nerve-Mediated Penile Erection in the Rabbit Model

Choi, Seong; Rhew, Hyun Yul; Goldstein, Irwin

Abstract

PURPOSE: Phosphodiesterase type 5 (PDE type 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE type 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, resulting ultimately in restoration of basal smooth muscle contractility and penile flaccidity. Sildenafil citrate and vardenafil hydrochloride have been shown to be potent, reversible and selective PDE type 5 inhibitors in penile smooth muscle cells with a Ki of 14.7 nM and 4.5 nM, respectively. The differences in the inhibition constants suggested that sildenafil and vardenafil may have different efficacy in facilitating penile erection in response to sexual stimulation. The objective of this study was to compare the time of onset and efficacy of vardenafil and sildenafil in facilitating/enhancing penile erection in an anesthetized rabbit model.
MATERIALS AND METHODS
Penile hemodynamics were assessed in male New Zealand White rabbits (3.5-4.0 kg) by intracavernosal pressure (ICP) monitoring before or after administration of varying doses of vardenafil or sildenafil. Drugs were administered intravenously or intracavernosally. Penile erections were elicited by submaximal electrical stimulation (2.5 or 6 Hz) of the pelvic nerve. ICP recordings were normalized to mean systemic systolic arterial pressure.
RESULTS
Intravenous administration of 1, 3, 10 or 30ng/kg of vardenafil or sildenafil facilitated pelvic nerve mediated penile erection in the anesthetized rabbits. ICP increased in a dose dependent fashion with both agents and reached peak response at about 5 minutes and lasted over 30 minutes at all doses tested. Intracavernosal injection of 10ng/kg of vardenafil or sldenafil enhanced pelvic nerve mediated erection at 2.5 Hz. At all doses investigated, vardenafil was more effective than sildenafil in facilitating pelvic nerve-mediated penile erection. Vardenafil had a significant effect on changes in systemic blood pressure when compared to sildenafil.
CONCLUSIONS
In this report, we demonstrate that vardenafil is more effective than sildenafil in potentiating penile erection, at equivalent doses as indicated by the maximal increase in ICP over time.