Silodosin (DB06207): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Silodosin is a highly selective alpha-1 adrenergic receptor antagonist, classified as a small molecule drug, primarily indicated for the symptomatic treatment of benign prostatic hyperplasia (BPH).[1] Its mechanism of action involves potent and specific blockade of the alpha-1A (

α1A​) adrenoceptor subtype, which is predominantly located in the smooth muscle of the prostate, bladder neck, and prostatic urethra.[3] This targeted antagonism leads to smooth muscle relaxation, resulting in reduced bladder outlet obstruction and significant improvement in both the voiding and storage symptoms associated with BPH.[2]

A defining feature of Silodosin is its exceptional uroselectivity, with a binding affinity for the α1A​ receptor that is over 160 times greater than its affinity for the α1B​ subtype found in vascular smooth muscle.[2] This pharmacological profile translates into a key clinical advantage: a minimal impact on blood pressure and a correspondingly low incidence of cardiovascular side effects, such as orthostatic hypotension, compared to less selective alpha-blockers.[7]

The pharmacokinetic profile of Silodosin is characterized by an oral bioavailability of approximately 32%, extensive metabolism primarily via UGT2B7 and to a lesser extent CYP3A4, and an elimination half-life of about 13 hours.[9] A major active metabolite, KMD-3213G, exhibits a longer half-life and achieves significantly higher plasma concentrations, contributing substantially to the overall therapeutic effect.[2]