Silodosin Treatment Research Articles

What are the factors contributing to failure in improvement of subjective symptoms following silodosin administration in patients with benign prostatic hyperplasia? investigation using a pressure‐flow study

To investigate the factors responsible for failure in improvement of subjective symptoms following silodosin treatment on the basis of findings of a pressure-flow study (PFS). A post hoc analysis of a prospective study to investigate the efficacy of silodosin in patients with BPH was conducted, and 104 patients were analyzed. The patients were administered silodosin 8 mg/day for 4 weeks. At the baseline and after treatment, subjective symptoms were evaluated using the IPSS and OABSS. A PFS was conducted to measure storage and voiding function. The patients were divided into two groups: good responders (GR), patients with 25% or more improvement in IPSS, and poor responders (PR), <25% improvement. The clinical and objective findings for the two groups were compared. The mean IPSS and OABSS significantly improved in GR, but no significant improvement was observed in PR. PFS analysis revealed that all voiding and storage function parameters improved significantly in GR. Although PR showed a significant improvement in the voiding function parameters, it did not show significant changes in the storage function. Involuntary detrusor contraction (IDC) resolved in 68.6% of the patients in GR and in only 30% of the patients in PR, thereby showing a significant difference in the remedial effect between the two groups. The findings suggest that insufficient improvement in storage function is a contributing factor to the failure in improvement of subjective symptoms after silodosin treatment in patients with BPH.

Effect of silodosin on detrusor overactivity in the male spontaneously hypertensive rat

Recently, several studies have suggested that detrusor overactivity (DO) is the result of bladder ischaemia. Hypertension could affect pelvic arterial blood flow, resulting in loss of smooth muscle in the bladder with resultant loss of bladder compliance. Spontaneously hypertensive rats are considered a valuable tool for exploring the pathogenesis of DO. Some reports indicate that α(1) adrenoceptor antagonists improve chronic ischaemia of the lower urinary tract in patients with LUTS, with concomitant improvement of their symptoms as well as improvement of DO through an increased bladder blood flow (BBF) in the rat with bladder outlet obstruction. However, the mechanism of improvement of silodosin on storage or irritative symptoms is not well investigated and is still unclear. Silodosin prevents hypertension-related DO in the SHR via several possible mechanisms. One possible mechanism of the efficacy of silodosin to the DO includes the improvement of the BBF. To investigate the effect of the α(1A) selective adrenoceptor antagonist, silodosin, on hypertension-related detrusor overactivity (DO) and its possible mechanism in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs received treatment with silodosin (100 µg/kg perorally) once daily for 6 weeks; vehicle-treated Wistar rats and vehicle-treated SHRs were used for our study. Six weeks after silodosin treatment, voiding functions were estimated by voiding behaviour and cystometric studies in all groups. The bladder blood flow was measured by the hydrogen clearance method, and tissue levels of nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of α1 adrenoceptor subtype mRNAs in the bladder were investigated by real-time PCR method. The SHRs showed significant increases in blood pressure, micturition frequency and tissue levels of NGF and CGRP in the bladder. Moreover, the SHRs showed significant decreases in bladder blood flow and single voided volume estimated by both voiding behaviour and cystometric studies compared with those in the Wistar rats. Six weeks of treatment with silodosin significantly ameliorated hypertension-related alterations of these variables with concomitant small changes of blood pressure. The expression levels of α1 adrenoceptor subtype mRNAs in the bladder were similar in all the groups and the rank order was α1A = α1D > α1B in all groups. However, there were no significant differences in the expressions of α(1A) adrenoceptor mRNAs between any groups. The data in the present study suggest that silodosin normalizes hypertension-related DO in SHRs, which could be related to its effect on the increased blood flow in the bladder.

Symptomatic and urodynamic responses in patients with reduced or no seminal emission during silodosin treatment for LUTS and BPH

Data from phase 3 studies (NCT00224107, NCT00224120) of silodosin for treatment of BPH symptoms were analyzed to examine the relationship between treatment efficacy and occurrence of abnormal ejaculation. Men aged ⩾50 years with International Prostate Symptom Scores (IPSS) ⩾13 and peak urinary flow rates (Qmax) of 4–15 ml s−1 received placebo or silodosin 8 mg once daily for 12 weeks. Silodosin-treated patients were stratified by absence or presence of ‘retrograde ejaculation' (RE). Groups were compared using analysis of covariance (for change from baseline) and responder analyses. Of the 466 patients receiving silodosin, 131 (28%) reported RE and 335 (72%) did not; 4 of the 457 patients receiving placebo (0.9%) reported RE. Most RE events in silodosin-treated patients (110/134; 82%) were reported as ‘orgasm with absence of seminal emission.' Silodosin-treated patients with (+) and without (−) RE showed significant improvement in IPSS, Qmax and quality of life versus placebo (P<0.02). RE+ patients versus RE− patients experienced numerically greater improvement, but differences were not statistically significant (P>0.05). For RE+ patients, the odds of achieving improvement of ⩾3 points in IPSS and ⩾3 ml s−1 in Qmax by study end were 1.75 times those for RE− patients (P=0.0127). Absence of seminal emission may predict superior treatment efficacy of silodosin in individual patients.

Short‐term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia

To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin-preceding group (4 weeks of twice-daily administration of silodosin at 4 mg, followed by 4 weeks of once-daily administration of tamsulosin at 0.2 mg) or a tamsulosin-preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients.

Silodosin in the Treatment of the Signs and Symptoms of Benign Prostatic Hyperplasia: A 9-Month, Open-label Extension Study

To evaluate long-term safety of the highly selective alpha(1A)-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia (BPH). Patients enrolled in this open-label extension study had completed 1 of 2 identical double-blind, placebo-controlled 12-week studies of silodosin treatment for symptomatic BPH. For 40 weeks, patients received silodosin 8 mg once daily with breakfast. Adverse events (AEs) were recorded to evaluate safety. Change in International Prostate Symptom Score was a secondary variable. Of the 661 participants, 435 (65.8%) completed the study; 431 patients (65.2%) experienced 924 AEs. No serious AEs that were considered drug-related by investigators occurred. AEs reported most often (percentage of patients) were retrograde ejaculation (20.9%), diarrhea (4.1%), and nasopharyngitis (3.6%). Orthostatic hypotension and dizziness occurred in 2.6% and 2.9% of patients, respectively. The percentage of patients with treatment-emergent AEs, stratified by preceding double-blind treatment (placebo or silodosin), was higher for de novo (previous treatment with placebo, 71.5%) than for continuing silodosin treatment (58.3%). More patients receiving de novo (7.5%) vs continuing treatment (1.9%) discontinued study participation because of retrograde ejaculation. Mean International Prostate Symptom Score change (standard deviation) from baseline to week 40 (observed cases) was -4.5 (6.7) for de novo treatment (P <.0001) and -1.6 (6.0) for continuing treatment (P <.01). Silodosin was well tolerated by men with BPH-related symptoms and was associated with low incidences of dizziness and orthostatic hypotension. Discontinuation because of retrograde ejaculation was more common among patients receiving silodosin de novo than in those who continued silodosin treatment.

Urodynamic effects of silodosin, a new α1A‐adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia

To investigate urodynamically the effects of silodosin, a new alpha(1A)-adrenoceptor-selective antagonist, in the treatment of benign prostatic hyperplasia (BPH). Thirty six male patients with BPH (69.9 +/- 7.3 years), who were referred as candidates for surgery, were treated with silodosin (4 mg twice daily). The total International Prostate Symptom Score (IPSS) was 20.7 +/- 7.4, maximum flow rate (Q(max)) was 6.7 +/- 3.0 ml/sec, and prostate volume was 45.6 +/- 24.5 ml. Total IPSS, storage and voiding symptom subscores and QOL score decreased significantly, and Q(max) increased significantly after 1-12 months of therapy (all P < 0.05). In urodynamic study (n = 29), maximum cystometric capacity increased significantly (P = 0.0027), and detrusor overactivity disappeared in 8 of 20 patients (40%) and improved (bladder capacity increased more than 50%) in 7 (35%) after the therapy. In pressure/flow studies (n = 27), the obstruction grade was improved in 15 patients (56%). Detrusor opening pressure, detrusor pressure at Q(max), bladder outlet obstruction index, and Schäfer's obstruction class decreased significantly after therapy (all P < 0.01). After 12 months, 16 patients (44%) are still on silodosin for 23.3 +/- 7.0 (range 12-36) months, and the improvements in IPSS and Q(max) were stable. Twenty patients withdrew because of insufficient effectiveness in 13 patients (12 patients underwent surgery), side effects in 3, and unknown reasons in 4. Silodosin appears to improve detrusor overactivity and obstruction grade in patients with BPH. With silodosin treatment, LUTS could be managed effectively for more than a year in at least 44% of the patients.

SILODOSIN, A NOVEL ALPHA1A AR-SUPER SELECTIVE ANTAGONIST, RAPIDLY IMPROVES BOTHERSOME NOCTURIA IN PATIENTS WHO ARE RESISTANT TO TAMUSULOSIN/NAFTOPIDIL

whether they did or did not report retrograde ejaculation (REj) as an adverse event (AE) during the study. RESULTS: (Table) Of the silodosin (SIL)-treated patients, 335 had no REj (-REj), while 131 had REj (+REj). Baseline IPSS and Qmax were comparable between groups. At 12 weeks, improvements in IPSS (LOCF) and Qmax (LOCF) were significantly greater for SIL(-REj) vs placebo and for SIL(+REj) vs placebo. Improvements in symptoms and peak flow rate were greater in the SIL(+REj) vs the SIL(-REj) group, with a trend toward significance for Qmax. CONCLUSIONS: The 28.1% experiencing retrograde ejaculation with silodosin treatment experienced greater improvement in symptoms and clinically meaningful greater improvement in peak flow rate compared with those not having this effect. This observation suggests that silodosin relaxes the smooth musculature of the lower urinary and genital tracts sufficiently to induce retrograde ejaculation, and that such superior relaxation results in greater objective efficacy in terms of unobstructing patients with LUTS secondary to BPH.