Management of benign prostatic hyperplasia with silodosin

Tomonori Yamanishi¹, Tomoya Mizuno¹, Takao Kamai¹, Ken-ichiro Yoshida¹, Ryuji Sakakibara², Tomoyuki Uchiyama³

¹Department of Urology, Dokkyo Medical University, Tochigi, Japan; ²Department of Neurology, Sakura Hospital, Toho University, Toho, Japan; ³Department of Neurology, Chiba University, Chiba, Japan

Abstract: It has been reported that blockade of α_1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α_1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α_1A-AR selective antagonist. Silodosin is highly selective for the α_1A-AR subtype, showing an affinity for the α_1A-AR that is 583- and 55.5-fold higher than its affinity for the α_1B- and α_1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia.

Keywords: alpha-blocker, silodosin, benign prostatic hyperplasia, lower urinary tract symptoms