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Francesco Montorsi - One of the best experts on this subject based on the ideXlab platform.
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Silodosin an update on efficacy safety and clinical indications in urology
Advances in Therapy, 2019Co-Authors: Luca Villa, Paolo Capogrosso, Umberto Capitanio, Alberto Martini, Alberto Briganti, Andrea Salonia, Francesco MontorsiAbstract:INTRODUCTION Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Phase III trials have already demonstrated the efficacy and safety of Silodosin in the treatment of patients bothered by lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). OBJECTIVE We aimed to describe the rationality for the use of Silodosin and to summarize the current literature on the use of Silodosin for the treatment of LUTS. METHODS PubMed and Web of Science were queried with the terms: 'Silodosin' in combination (AND) with the terms 'lower urinary tract symptoms', 'LUTS', 'pathophysiology', 'symptoms' OR 'therapy'. Studies published in the last 10 years (2007-2017) in adults and core clinical journals in English were included. RESULTS Silodosin 8 mg once-daily was superior to placebo in improving IPSS total score, voiding subscore, storage subscore and QoL score, and at least as effective as tamsulosin 0.4 mg once-daily in all the efficacy analyses. In addition, studies assessing the effect on urodynamic parameters showed that Silodosin determined a higher improvement in the bladder outlet obstruction index compared to other alpha1 adrenergic receptor antagonists. Concerning the safety profile, long-term data (after 9 months of treatment) confirmed the limited effect of Silodosin on the cardiovascular and gastrointestinal systems. Although ejaculatory disorders represented the main complaint of patients taking Silodosin, the discontinuation rate due to this condition remained low even in a long-term follow-up study (7.5%). Encouraging findings showed that Silodosin may be administered as a medical expulsive therapy for promoting spontaneous stone passage of distal ureteral stones < 10 mm, to relieve LUTS in patients who underwent prostate cancer brachytherapy and to increase the likelihood of successful trials without a catheter in patients experiencing acute urinary retention. CONCLUSION Silodosin is one of the drugs approved for the treatment of BPH, being highly effective in improving not only LUTS but also urodynamic parameter impairments secondary to BPH. Moreover, it has shown efficacy as medical expulsive therapy for distal ureteral stones in previous prospective randomized trials. FUNDING Sponsorship for this study and article processing charges were funded by Recordati.
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Silodosin: An Update on Efficacy, Safety and Clinical Indications in Urology
Advances in Therapy, 2019Co-Authors: Luca Villa, Paolo Capogrosso, Umberto Capitanio, Alberto Martini, Alberto Briganti, Andrea Salonia, Francesco MontorsiAbstract:Introduction Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Phase III trials have already demonstrated the efficacy and safety of Silodosin in the treatment of patients bothered by lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Objective We aimed to describe the rationality for the use of Silodosin and to summarize the current literature on the use of Silodosin for the treatment of LUTS. Methods PubMed and Web of Science were queried with the terms: ‘Silodosin’ in combination (AND) with the terms ‘lower urinary tract symptoms’, ‘LUTS’, ‘pathophysiology’, ‘symptoms’ OR ‘ therapy’. Studies published in the last 10 years (2007–2017) in adults and core clinical journals in English were included. Results Silodosin 8 mg once-daily was superior to placebo in improving IPSS total score, voiding subscore, storage subscore and QoL score, and at least as effective as tamsulosin 0.4 mg once-daily in all the efficacy analyses. In addition, studies assessing the effect on urodynamic parameters showed that Silodosin determined a higher improvement in the bladder outlet obstruction index compared to other alpha1 adrenergic receptor antagonists. Concerning the safety profile, long-term data (after 9 months of treatment) confirmed the limited effect of Silodosin on the cardiovascular and gastrointestinal systems. Although ejaculatory disorders represented the main complaint of patients taking Silodosin, the discontinuation rate due to this condition remained low even in a long-term follow-up study (7.5%). Encouraging findings showed that Silodosin may be administered as a medical expulsive therapy for promoting spontaneous stone passage of distal ureteral stones
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individual patient data from registrational trials of Silodosin in the treatment of non neurogenic male lower urinary tract symptoms luts associated with benign prostatic hyperplasia bph subgroup analyses of efficacy and safety data
BJUI, 2015Co-Authors: Giacomo Novara, Christopher R Chapple, Francesco MontorsiAbstract:Objective To evaluate efficacy and safety of Silodosin in a pooled analysis of individual patient data from three registrational randomised controlled trials (RCTs) comparing Silodosin and placebo in patients with lower urinary tract symptoms (LUTS). Patients and Methods A pooled analysis of 1494 patients from three 12-week, multicentre, double-blind, placebo-controlled phase III RCTs was performed. Efficacy and safety data were assessed across patients with different baseline characteristics. Results Silodosin was significantly more effective than placebo in improving all International Prostate Symptom Score (IPSS)-related parameters, and maximum urinary flow rate (Qmax) regardless of patients age (P < 0.041). Comparing the efficacy of Silodosin in the different age groups, there were no differences for all the IPSS-related parameters, whereas Qmax improvement was slightly higher in patients aged <65 years (P = 0.009). Silodosin was significantly more effective than placebo in reducing all IPSS-related parameters regardless of baseline IPSS (P ≤ 0.001). Similarly, Silodosin was more effective than placebo in improving IPSS-related parameters regardless of baseline Qmax (P ≤ 0.02). Silodosin was associated with significantly higher adverse event (AE) rates, compared with placebo, in all patient subgroups, with retrograde ejaculation being the most common. Prevalence of dizziness, orthostatic hypotension, and discontinuation rate was similar with Silodosin and placebo in most patient subgroups. Conclusions We analysed the efficacy and safety of Silodosin in several patient subgroups, showing that Silodosin was more effective than placebo in improving all IPSS-related parameters in all patient subgroups, whereas AEs were similar. Notably, cardiovascular AEs were not higher in patients taking antihypertensive drugs or with mild renal function impairment. Discontinuation rates due to AEs were lower in elderly patients.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve mediated contractions of human and rat isolated prostates
European Journal of Pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P<0.05), 40-58% (10 nM Silodosin+1 µM tadalafil; P<0.001-0.05), 56-67% (100 nM Silodosin+10 µM tadalafil; P<0.01-0.05), and 33-55% (1 µM Silodosin+100 µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as Silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates
European journal of pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P
Luca Villa - One of the best experts on this subject based on the ideXlab platform.
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Silodosin: An Update on Efficacy, Safety and Clinical Indications in Urology
Advances in Therapy, 2019Co-Authors: Luca Villa, Paolo Capogrosso, Umberto Capitanio, Alberto Martini, Alberto Briganti, Andrea Salonia, Francesco MontorsiAbstract:Introduction Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Phase III trials have already demonstrated the efficacy and safety of Silodosin in the treatment of patients bothered by lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Objective We aimed to describe the rationality for the use of Silodosin and to summarize the current literature on the use of Silodosin for the treatment of LUTS. Methods PubMed and Web of Science were queried with the terms: ‘Silodosin’ in combination (AND) with the terms ‘lower urinary tract symptoms’, ‘LUTS’, ‘pathophysiology’, ‘symptoms’ OR ‘ therapy’. Studies published in the last 10 years (2007–2017) in adults and core clinical journals in English were included. Results Silodosin 8 mg once-daily was superior to placebo in improving IPSS total score, voiding subscore, storage subscore and QoL score, and at least as effective as tamsulosin 0.4 mg once-daily in all the efficacy analyses. In addition, studies assessing the effect on urodynamic parameters showed that Silodosin determined a higher improvement in the bladder outlet obstruction index compared to other alpha1 adrenergic receptor antagonists. Concerning the safety profile, long-term data (after 9 months of treatment) confirmed the limited effect of Silodosin on the cardiovascular and gastrointestinal systems. Although ejaculatory disorders represented the main complaint of patients taking Silodosin, the discontinuation rate due to this condition remained low even in a long-term follow-up study (7.5%). Encouraging findings showed that Silodosin may be administered as a medical expulsive therapy for promoting spontaneous stone passage of distal ureteral stones
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Silodosin an update on efficacy safety and clinical indications in urology
Advances in Therapy, 2019Co-Authors: Luca Villa, Paolo Capogrosso, Umberto Capitanio, Alberto Martini, Alberto Briganti, Andrea Salonia, Francesco MontorsiAbstract:INTRODUCTION Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Phase III trials have already demonstrated the efficacy and safety of Silodosin in the treatment of patients bothered by lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). OBJECTIVE We aimed to describe the rationality for the use of Silodosin and to summarize the current literature on the use of Silodosin for the treatment of LUTS. METHODS PubMed and Web of Science were queried with the terms: 'Silodosin' in combination (AND) with the terms 'lower urinary tract symptoms', 'LUTS', 'pathophysiology', 'symptoms' OR 'therapy'. Studies published in the last 10 years (2007-2017) in adults and core clinical journals in English were included. RESULTS Silodosin 8 mg once-daily was superior to placebo in improving IPSS total score, voiding subscore, storage subscore and QoL score, and at least as effective as tamsulosin 0.4 mg once-daily in all the efficacy analyses. In addition, studies assessing the effect on urodynamic parameters showed that Silodosin determined a higher improvement in the bladder outlet obstruction index compared to other alpha1 adrenergic receptor antagonists. Concerning the safety profile, long-term data (after 9 months of treatment) confirmed the limited effect of Silodosin on the cardiovascular and gastrointestinal systems. Although ejaculatory disorders represented the main complaint of patients taking Silodosin, the discontinuation rate due to this condition remained low even in a long-term follow-up study (7.5%). Encouraging findings showed that Silodosin may be administered as a medical expulsive therapy for promoting spontaneous stone passage of distal ureteral stones < 10 mm, to relieve LUTS in patients who underwent prostate cancer brachytherapy and to increase the likelihood of successful trials without a catheter in patients experiencing acute urinary retention. CONCLUSION Silodosin is one of the drugs approved for the treatment of BPH, being highly effective in improving not only LUTS but also urodynamic parameter impairments secondary to BPH. Moreover, it has shown efficacy as medical expulsive therapy for distal ureteral stones in previous prospective randomized trials. FUNDING Sponsorship for this study and article processing charges were funded by Recordati.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve mediated contractions of human and rat isolated prostates
European Journal of Pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P<0.05), 40-58% (10 nM Silodosin+1 µM tadalafil; P<0.001-0.05), 56-67% (100 nM Silodosin+10 µM tadalafil; P<0.01-0.05), and 33-55% (1 µM Silodosin+100 µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as Silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates
European journal of pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P
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Effects by Silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters
British Journal of Pharmacology, 2013Co-Authors: Luca Villa, Roberta Buono, Nicola Fossati, Patrizio Rigatti, Francesco Montorsi, Fabio Benigni, Petter HedlundAbstract:Background and Purpose 1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the 1A-AR selective antagonist Silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. Experimental Approach After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the 1-AR antagonists were given intravenously. Effects by the 1-AR antagonists on isolated human and rat ureters were studied in organ baths. Key Results Intravenous Silodosin (0.10.3mgkg1) or prazosin (0.030.1mgkg1) reduced obstruction-induced increases in intraluminal ureter pressures by 2137% or 1840% respectively. Corresponding effects by tamsulosin (0.01 or 0.03mgkg1) were 920%. Silodosin, prazosin and tamsulosin reduced MAP by 1012%, 2526% (P < 0.05), or 1825% (P < 0.05) respectively. When effects by the 1A-AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, Silodosin had six- to eightfold and 2.5- to eightfold better efficacy than tamsulosin or prazosin respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. Conclusions and Implications Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored.
Petter Hedlund - One of the best experts on this subject based on the ideXlab platform.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve mediated contractions of human and rat isolated prostates
European Journal of Pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P<0.05), 40-58% (10 nM Silodosin+1 µM tadalafil; P<0.001-0.05), 56-67% (100 nM Silodosin+10 µM tadalafil; P<0.01-0.05), and 33-55% (1 µM Silodosin+100 µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as Silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.
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Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates
European journal of pharmacology, 2014Co-Authors: Roberta Buono, Luca Villa, Francesco Montorsi, Fabio Benigni, Alberto Briganti, Massimo Freschi, Giovanni La Croce, Marco Moschini, Fabio Castiglione, Petter HedlundAbstract:Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of Silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of Silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination Silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM Silodosin+100 nM tadalafil; P
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Effects by Silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters
British Journal of Pharmacology, 2013Co-Authors: Luca Villa, Roberta Buono, Nicola Fossati, Patrizio Rigatti, Francesco Montorsi, Fabio Benigni, Petter HedlundAbstract:Background and Purpose 1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the 1A-AR selective antagonist Silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. Experimental Approach After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the 1-AR antagonists were given intravenously. Effects by the 1-AR antagonists on isolated human and rat ureters were studied in organ baths. Key Results Intravenous Silodosin (0.10.3mgkg1) or prazosin (0.030.1mgkg1) reduced obstruction-induced increases in intraluminal ureter pressures by 2137% or 1840% respectively. Corresponding effects by tamsulosin (0.01 or 0.03mgkg1) were 920%. Silodosin, prazosin and tamsulosin reduced MAP by 1012%, 2526% (P < 0.05), or 1825% (P < 0.05) respectively. When effects by the 1A-AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, Silodosin had six- to eightfold and 2.5- to eightfold better efficacy than tamsulosin or prazosin respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. Conclusions and Implications Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored.
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Silodosin From Bench to Bedside: Selectivity, Safety, and Sustained Efficacy
European Urology Supplements, 2011Co-Authors: Andrea Russo, Petter Hedlund, Francesco MontorsiAbstract:Abstract Context Silodosin is the α 1– adrenoceptor (AR) antagonist with the highest selectivity for the α 1A -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? Objective Analyse information on the preclinical selectivity profile of Silodosin in relation to clinical efficacy and safety. Evidence acquisition A 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 synthesis Silodosin exhibits high selectivity for the α 1A 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. Conclusions Both 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 α 1A -AR subtype. Silodosin has a rapid onset of action and a sustained efficacy on LUTS due to BPH.
Masaki Yoshida - One of the best experts on this subject based on the ideXlab platform.
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Post-Marketing Surveillance of Silodosin in Patients with Benign Prostatic Hyperplasia and Poor Response to Existing Alpha-1 Blockers: The SPLASH Study
Drugs in R&D, 2019Co-Authors: Hiroshi Takahashi, Shinichi Kubono, Takehiko Taneyama, Kiyotoshi Kuramoto, Hideki Mizutani, Noriko Tanaka, Masaki YoshidaAbstract:Objectives Our objective was to investigate the effectiveness and safety of Silodosin in patients with benign prostatic hyperplasia (BPH) who switched to Silodosin from another α_1 blocker because of inadequate response. Methods This was a prospective observational study conducted at 715 medical facilities in Japan in patients with BPH who received an α_1 blocker other than Silodosin for at least 3 months but had experienced unsatisfactory treatment outcomes. Patients completed questionnaires, including the International Prostate Symptom Score (IPSS), quality of life (QOL) score and Overactive Bladder Symptom Score (OABSS) at baseline (time of switching) and after 3 months of treatment with Silodosin. Results Overall, 3355 patients were assessed for safety and 3144 patients for effectiveness. Mean ± standard deviation age was 73.1 ± 8.2 years, and most patients had been receiving tamsulosin (53.6%) or naftopidil (45.5%) before Silodosin. Silodosin was well tolerated, with an overall incidence of adverse drug reactions of 8.1% and no unexpected safety signals. Significant improvements were observed after switching to Silodosin in all effectiveness outcome measures, including total IPSS, all IPSS subscale scores, QOL score, total OABSS, all OABSS subscale scores and residual urine volume. Significant improvements in total IPSS were seen in patients who had been receiving tamsulosin or naftopidil before switching and in almost all other patient subgroups, with the exception of patients with mild symptoms (total IPSS ≤ 7) at baseline. Conclusions This post-marketing analysis indicates that switching to Silodosin from tamsulosin or naftopidil significantly improved symptoms associated with BPH, and Silodosin was well tolerated in Japanese patients.
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Post-Marketing Surveillance of Silodosin in Patients with Benign Prostatic Hyperplasia and Poor Response to Existing Alpha-1 Blockers: The SPLASH Study.
Drugs in R&D, 2019Co-Authors: Hiroshi Takahashi, Shinichi Kubono, Takehiko Taneyama, Kiyotoshi Kuramoto, Hideki Mizutani, Noriko Tanaka, Masaki YoshidaAbstract:Our objective was to investigate the effectiveness and safety of Silodosin in patients with benign prostatic hyperplasia (BPH) who switched to Silodosin from another α1 blocker because of inadequate response. This was a prospective observational study conducted at 715 medical facilities in Japan in patients with BPH who received an α1 blocker other than Silodosin for at least 3 months but had experienced unsatisfactory treatment outcomes. Patients completed questionnaires, including the International Prostate Symptom Score (IPSS), quality of life (QOL) score and Overactive Bladder Symptom Score (OABSS) at baseline (time of switching) and after 3 months of treatment with Silodosin. Overall, 3355 patients were assessed for safety and 3144 patients for effectiveness. Mean ± standard deviation age was 73.1 ± 8.2 years, and most patients had been receiving tamsulosin (53.6%) or naftopidil (45.5%) before Silodosin. Silodosin was well tolerated, with an overall incidence of adverse drug reactions of 8.1% and no unexpected safety signals. Significant improvements were observed after switching to Silodosin in all effectiveness outcome measures, including total IPSS, all IPSS subscale scores, QOL score, total OABSS, all OABSS subscale scores and residual urine volume. Significant improvements in total IPSS were seen in patients who had been receiving tamsulosin or naftopidil before switching and in almost all other patient subgroups, with the exception of patients with mild symptoms (total IPSS ≤ 7) at baseline. This post-marketing analysis indicates that switching to Silodosin from tamsulosin or naftopidil significantly improved symptoms associated with BPH, and Silodosin was well tolerated in Japanese patients.
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Comparison of Silodosin versus Tadalafil in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.
Lower urinary tract symptoms, 2017Co-Authors: Masaki Yoshida, Hideki Origasa, Narihito SekiAbstract:Objectives To compare the efficacy and safety of Silodosin versus tadalafil for treating lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Methods After informed consent, patients with LUTS/BPH were randomized in a 1:1 ratio to receive Silodosin 8 mg/day or tadalafil 5 mg/day for 8 weeks (Period 1). Patients treated with tadalafil entered an exploratory phase and received Silodosin or tadalafil for another 8 weeks. The primary efficacy endpoint was the change in the total International Prostate Symptom Score (IPSS) with Period 1 treatment. Results Both Silodosin and tadalafil demonstrated statistically significant improvement in IPSS total symptom score, with a mean ± standard deviation change of −10.1 ± 6.4 (P < 0.0001) and −8.0 ± 6.3 (P < 0.0001), respectively. The former reduction was significantly greater than the latter (P = 0.0277). Adverse drug reactions occurred at a rate of 23.4% with Silodosin and 8.4% with tadalafil. No serious adverse drug reactions were documented, suggesting that both drugs were well tolerated. Moreover, results of Period 2 showed that switching to Silodosin from tadalafil achieved a faster onset of improvements in IPSS Quality of Life Index score and total Overactive Bladder Symptom Score. Conclusions Silodosin achieved significantly greater improvement than tadalafil, with a higher incidence of adverse drug reactions. The risk-benefit profiles obtained in this study will provide useful information for optimal pharmacological treatment of LUTS/BPH. Our results suggest that Silodosin can be one of the first-line therapies for rapid and efficient relief in patients with LUTS/BPH.
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New clinical evidence of Silodosin, an α(1A) selective adrenoceptor antagonist, in the treatment for lower urinary tract symptoms.
International journal of urology : official journal of the Japanese Urological Association, 2012Co-Authors: Masaki Yoshida, Yukio Homma, Junzo Kudoh, Kazuki KawabeAbstract:Lower urinary tract symptoms associated with benign prostatic hyperplasia are highly prevalent in older men. Pharmacological treatment is the first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. The first choice in the pharmacological treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia is the α(1) -adrenoceptor antagonists. Many α(1) -adrenoceptor antagonists are available in the world. Silodosin is an α(1) -adrenoceptor antagonist developed by Kissei Pharmaceutical, and has a specific selectivity for the α(1A-) adrenoceptor subtype. By antagonizing α(1A) -adrenoceptor in the prostate and urethra, Silodosin causes smooth muscle relaxation in the lower urinary tract. As a result of the high affinity for the α(1A) -adrenoceptor than for the α(1B) -adrenoceptor, Silodosin minimizes the propensity for blood pressure-related adverse effects caused by blockade of α(1B) -adrenoceptor. The efficacy and safety of Silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia was first reported by Japanese investigators in 2006. At present, Silodosin is used in many countries. In the present review, we summarize the new clinical evidence for lower urinary tract symptoms associated with benign prostatic hyperplasia and introduce the data supporting the new clinical indications of Silodosin.
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Safety and efficacy of Silodosin for the treatment of benign prostatic hyperplasia
Clinical interventions in aging, 2011Co-Authors: Masaki Yoshida, Yukio Homma, Junzo Kudoh, Kazuki KawabeAbstract:Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α1-adrenergic receptor antagonists. Silodosin is a new α1-adrenergic receptor antagonist that is selective for the α1A-adrenergic receptor. By antagonizing α1A-adrenergic receptors in the prostate and urethra, Silodosin causes smooth muscle relaxation in the lower urinary tract. Since Silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α1B-adrenergic receptor blockade. In the clinical studies, patients receiving Silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of Silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, Silodosin, a novel selective α1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of Silodosin in the treatment of LUTS associated with BPH.
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efficacy and safety of Silodosin in the medical expulsion therapy for distal ureteral calculi a systematic review and meta analysis
British Journal of Clinical Pharmacology, 2016Co-Authors: Wei Huang, Peng Xue, Huantao Zong, Yong ZhangAbstract:Aims Using a selective α-adrenoceptor blocker for medical expulsive therapy (MET) is an effective treatment approach widely used for ureteral stones. The aim of the review was to assess the efficacy and safety of Silodosin in medical expulstion therapy compared with placebo and tamsulosin. Methods A systematic search was performed in PubMed, Cochrane Library and Embase to identify randomized controlled trials that compared Silodosin with a placebo or tamsulosin for ureteral calculi. Results Eight publications involving a total of 1048 patients were used in the analysis, which compared Silodosin with placebo and tamsulosin. We found that Silodosin was effective in treating ureteral calculi in our meta-analysis and was superior to tamsulosin in its efficacy. The expulsion rate of all ureteral stones (OR 1.59, 95% CI 1.08, 2.36, P = 0.02), the expulsion rate of distal ureteral stones (OR 2.82, 95% CI 1.70, 4.67, P < 0.0001) and the expulsion time (days) of distal ureteral stones (standard mean difference (SMD) −4.71, 95% CI −6.60, −2.83, P < 0.00001) indicated that Silodosin was more effective than the placebo. Moreover, expulsion rate (OR 2.54, 95% CI 1.70, 3.78, P < 0.00001), expulsion time (days) (SMD −2.64, 95% CI −3.64, −1.64, P < 0.00001) and pain episodes (P < 0.00001) indicated that Silodosin was more effective than the tamsulosin. Even though Silodosin had a significant increase in abnormal ejaculation compared with tamsulosin, no significant differences were observed for complications (OR 1.00, 95% CI 0.58, 1.74, P = 1.00). Conclusions This meta-analysis indicated that Silodosin was superior to placebo or tamsulosin in the efficacy for distal ureteral calculi with better control of pain. The safety profile of Silodosin was similar to tamsulosin though retrograde ejaculation was worse for Silodosin use. We conclude that Silodosin might have potential as a MET for ureteral stones.
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Efficacy and safety of Silodosin in the medical expulsion therapy for distal ureteral calculi: a systematic review and meta‐analysis
British journal of clinical pharmacology, 2015Co-Authors: Wei Huang, Peng Xue, Huantao Zong, Yong ZhangAbstract:Aims Using a selective α-adrenoceptor blocker for medical expulsive therapy (MET) is an effective treatment approach widely used for ureteral stones. The aim of the review was to assess the efficacy and safety of Silodosin in medical expulstion therapy compared with placebo and tamsulosin. Methods A systematic search was performed in PubMed, Cochrane Library and Embase to identify randomized controlled trials that compared Silodosin with a placebo or tamsulosin for ureteral calculi. Results Eight publications involving a total of 1048 patients were used in the analysis, which compared Silodosin with placebo and tamsulosin. We found that Silodosin was effective in treating ureteral calculi in our meta-analysis and was superior to tamsulosin in its efficacy. The expulsion rate of all ureteral stones (OR 1.59, 95% CI 1.08, 2.36, P = 0.02), the expulsion rate of distal ureteral stones (OR 2.82, 95% CI 1.70, 4.67, P
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Silodosin efficacy and safety in the treatment of BPH : a meta-analysis
Chinese Journal of Urology, 2013Co-Authors: Yuanshan Cui, Huantao Zong, Huilei Yan, Yong ZhangAbstract:Objective To evaluate the efficacy and safety of Silodosin in the treatment of benign prostatic hyperplasia (BPH).Methods Randomized controlled trials (RCT) on the efficacy and safety of Silodosin for the treatment of BPH were retrieved from Medline (1966-2012),Embase (1988-2012),Cochrane liberary,CMCC (1979-2012),CNK1 (1979-2012) and the quality of the included RCTs were evaluated using Cochrane systematic evaluation to analyze the data statistically using Rev Man 5.1.0 software.Results Six RCTs involving 2543 participants were included for the meta-analysis.Results of analysis showed that Silodosin was effective in the treatment of BPH in term of total international prostate symptom score (IPSS) (standard mean difference (SMD) =2.92,95 ％ CI =2.19-3.65,P ＜ 0.05),voiding symptom score (SMD =1.92,95％ CI =1.44-2.39,P ＜0.05),storage symptom score (SMD =0.92,95％ CI=0.60-1.24,P ＜0.05),and maximum flow rate (Qmax) score (SMD =1.56,95％ CI=1.38-1.75,P ＜ 0.05),compared with the placebo.Silodosin 8 mg was more effective than tamsulosin 0.2 mg in term of IPSS-related parameters and Qmax (P ＜ 0.05).Silodosin 8mg and tamsulosin 0.4 mg were similarly effective in all the efficacy analyses.Abnormal ejaculation was less common with tamsulosin 0.2 mg and 0.4mg (P＜0.05); overall adverse events were similar with tamsulosin 0.2 and 0.4 mg (P ＜0.05).Conclusions Silodosin was significantly more effective than placebo and tamsulosin 0.2 mg in improving symptoms and as effective as tamsulosin 0.4 mg.For adverse events,abnormal ejaculation was more common with Silodosin. Key words: Silodosin; Benign prostate hyperplasia; Meta-analysis; Randomized controlled trials
