Duration of Action of Silodosin (KMD-3213) against Phenylephrine-induced Increase in Intraurethral Pressure in Rats

Abstract

The duration of action of Silodosin (KMD-3213) against the phenylephrine-induced increase in intraurethral pressure in urethane-anesthetized rats was compared with that of tamsulosin hydrochloride. Silodosin, tamsulosin, or vehicle was orally administered to fasted male rats. Then, under urethane anesthesia, a cannula was inserted into the prostatic urethra. Phenylephrine, at a dose of 30 microg/kg, was infused (infusion rate: 36 ml/h; infusion time: 100 s/kg) via the femoral vein at 12 h, 18 h, or 24 h after administration of the study drug, and the intraurethral pressure in the prostate region was measured. Although the plasma silodosin concentration would have resolved within a few hours, silodosin significantly inhibited the phenylephrine-induced increase in intraurethral pressure (versus the vehicle-treated group) at 12 h, 18 h, and 24 h after its oral administration (at doses of 100 microg/kg and above, 1000 microg/kg and above, and 3000 microg/kg, respectively). On the other hand, tamsulosin hydrochloride showed no inhibitory action at 24 h after its oral administration at doses up to 3000 microg/kg. Thus, silodosin inhibits the phenylephrine-induced increase in intraurethral pressure for a longer time than tamsulosin hydrochloride.