Silodosin From Bench to Bedside: Selectivity, Safety, and Sustained Efficacy

ContextSilodosin is the α1–adrenoceptor (AR) antagonist with the highest selectivity for the α1A-AR subtype that is available for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). How do preclinical findings translate into clinical effect?ObjectiveAnalyse information on the preclinical selectivity profile of silodosin in relation to clinical efficacy and safety.Evidence acquisitionA Medline search for published articles on silodosin in preclinical and clinical studies was conducted. Information was also acquired from documents published by the European Medicines Agency.Evidence synthesisSilodosin exhibits high selectivity for the α1A subtype of the adrenoceptor, and it also displays selectivity for the lower urinary tract and prostate versus vascular functions as assessed in studies of isolated tissues, animal models, and patients. Silodosin causes symptom relief within days and is superior to placebo and noninferior to tamsulosin in reducing symptoms in patients with BPH. The effects of silodosin were sustained for 40–52 wk in open-label extension studies of 1170 patients. The safety and tolerability of silodosin are excellent. Silodosin more frequently causes abnormal ejaculation than placebo or tamsulosin, although only a minority of the patients discontinues treatment due to this adverse event.ConclusionsBoth preclinical and clinical studies support the contention that silodosin has high uroselectivity and a positive cardiovascular safety profile, likely related to its selectivity for the α1A-AR subtype. Silodosin has a rapid onset of action and a sustained efficacy on LUTS due to BPH.