Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability

Research and Reports in Urology Dovepress open access to scientific and medical research Review Research and Reports in Urology downloaded from https://www.dovepress.com/ by 54.38.22.117 on 13-Jul-2018 For personal use only. Open Access Full Text Article Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability This article was published in the following Dove Press journal: Research and Reports in Urology 26 September 2014 Number of times this article has been viewed Hee Ju Cho Tag Keun Yoo Department of Urology, Eulji Hospital, Eulji University School of Medicine, Seoul, Korea Introduction and background Correspondence: Tag Keun Yoo Department of Urology, Eulji Hospital, Eulji University School of Medicine, 280-1, Hagye 1-dong, Nowon-gu, Seoul 139-872, Korea Tel +82 2 970 8305 Fax +82 2 970 8517 Email Silodosin, a highly selective α1-adrenergic receptor antagonist for the treatment of lower urinary tract symptoms (LUTS),1 was developed in 1995 under its original name, KMD-3213.2 Thereafter, several in vitro studies in humans have proved the uroselectivity of silodosin, which affects the contraction of the prostatic smooth muscle,3,4 to be greater than that of tamsulosin and naftopidil.5 Silodosin was approved in Japan in 2006, more recently it has received approval in the United States, Europe, and Korea.6 We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify research articles, preclinical studies, and systematic and general reviews that discuss the pharmacological features, safety, and efficacy of silodosin. Pharmacodynamics and pharmacokinetics Receptor binding studies show that silodosin has a very strong affinity for the α1Aadrenergic receptor. For example, the affinity of silodosin for the α1A-adrenergic 113 submit your manuscript | www.dovepress.com Research and Reports in Urology 2014:6 113–119 Dovepress © 2014 Cho and Yoo. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/RRU.S41618 Powered by TCPDF (www.tcpdf.org) Abstract: α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society. Keywords: α1A-adrenoceptor antagonist, silodosin, benign prostatic hyperplasia, lower urinary tract symptoms Dovepress Research and Reports in Urology downloaded from https://www.dovepress.com/ by 54.38.22.117 on 13-Jul-2018 For personal use only. Cho and Yoo receptor is 162 times higher than that for the α1B-adrenergic receptor, and 55 times higher than that for the α1Dadrenergic receptor.7 Other studies that address native organ selectivity and α1-adrenoceptor sensitivity reveal that the sensitivity of silodosin for the prostate in Japanese white rabbits was 280 times greater than that for the α1B-adrenergic receptor-rich spleen in Sprague Dawley rats, and approximately 50 times greater than that for the α1D-adrenergic receptor-rich thoracic aorta in the same species. The selectivity of silodosin for the urethra and bladder trigone is comparable to the prostate.7,8 The uroselectivity of silodosin has also been shown in in vivo studies in Sprague Dawley rats. After the administration of anesthesia and then phenylephrine, which increased the intraurethral pressure, several α-blockers, including silodosin, tamsulosin, naftopidil, and prazosin were injected to evaluate their effects on the intraurethral pressure and mean blood pressure. Although silodosin suppressed the intraurethral pressure only, tamsulosin hydrochloride (HCl) can affect the intraurethral pressure and mean arterial pressure at a dose similar to that of silodosin.9 The ID50 (defined as the dose at which intraurethral pressure is suppressed by 50%) (µg/kg), which is defined as the dose that can suppress the increase in intraurethral pressure by 50%, was 0.932 for silodosin, 0.400 for tamsulosin HCl, 361 for naftopidil, and 4.04 for prazosin. The ED15 (defined as the dose at which the mean blood pressure is decreased by 15%) (µg/kg), which is defined as the dose that can decrease the mean arterial pressure by 15%, was 10.9 for silodosin, 0.895 for tamsulosin HCl, 48.1 for naftopidil, and 0.792 for prazosin. Uroselectivity, which was calculated by ED15/ID50, was highest in the silodosin group (11.7). The ratios were 2.24, 0.133, and 0.196 for tamsulosin, naftopidil, and prazosin, respectively (Table 1).9 Silodosin is metabolized by UDP-glucuronosyltransferase2B7 (UGT2B7), alcohol and aldehyde dehydrogenases, and cytochrome P450 3A4 (CYP3A4) pathways, and is excreted in urine (34%) and feces (55%).10 Therefore, clinicians should not prescribe silodosin for patients who are also receiving CYP3A4 inhibitors such as ketoconazole and ritonavir, however, it can be prescribed for those taking moderate CYP3A4 inhibitors, such as diltiazem, or phosphodiesterase-5 inhibitors without significant changes in blood pressure and (...truncated)