ラットのフェニレフリン誘発尿道内圧上昇に対するシロドシン(KMD-3213)の作用持続性(<特集>シロドシン)

概要

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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 30μg/kg, was infused (infusion rate: 36ml/h; infusion time: 100s/kg) via the femoral vein at 12h, 18h, or 24h 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 12h, 18h, and 24h after its oral administration (at doses of 100μg/kg and above, 1000μg/kg and above, and 3000μg/kg, respectively). On the other hand, tamsulosin hydrochloride showed no inhibitory action at 24h after its oral administration at doses up to 3000μg/kg. Thus, silodosin inhibits the phenylephrine-induced increase in intraurethral pressure for a longer time than tamsulosin hydrochloride.
2006-03-01