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Introduction: The use of a ureteral access sheath (UAS) during ureteroscopy (URS) has been associated with the risk for ureteral injuries. Preoperative administration of α1-blockers presents a potential mitigator of such lesions by inducing ureteral relaxation, which may also contribute to improving other surgical outcomes. Methods: A comprehensive literature search was conducted across MEDLINE, Embase, and Cochrane databases for studies comparing preoperative α1-blockers administration vs its non-use in adult patients without pre-stenting undergoing URS. Binary outcomes were evaluated using risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was measured with the Cochran's Q test, I2 statistics, and prediction intervals (PIs). A DerSimonian and Laird random-effects model was utilized for all outcomes. Results: Eleven studies encompassing 1074 patients undergoing URS were included, of whom 522 (48.60%) received α1-blockers before the procedure. Preoperative α1-blockers were associated with a reduction in significant ureteral injuries (RR 0.30; 95% CI 0.17–0.53; I2 = 6%; PI 0.10–0.88) and an increase in mean successful UAS insertion (OR 2.14; 95% CI 1.08–4.23; I2 = 23%; PI 0.51–8.93). In patients undergoing exclusively ureteroscopy lithotripsy (URSL), the medications also reduced total complications (RR 0.62; 95% CI 0.46–0.84; I2 = 0%) and complications graded Clavien–Dindo III or higher (RR 0.16; 95% CI 0.04–0.69; I2 = 0%), but no significant difference between groups was found in the stone-free rate (RR 1.10; 95% CI 0.86–1.40; I2 = 91%; PI 0.47–2.59). Conclusion: Preoperative α1-blockers were linked to a decrease in significant ureteral injuries with UAS use and fewer complications during URSL procedures. However, their impact on the successful insertion of a UAS remains uncertain. Consideration of administering preoperative α1-blockers in non-stented adult patients undergoing URS with UAS is advisable. [ABSTRACT FROM AUTHOR]

Abstract Objectives This work aims to determine the efficacy and safety of preoperative alpha‐blocker therapy on ureteroscopy (URS) outcomes. Methods In this systematic review and meta‐analysis of randomised trials of URS with or without preoperative alpha‐blocker therapy, outcomes included the need for ureteral dilatation, stone access failure, procedure time, residual stone rate, hospital stay, and complications. Residual stone rates were reported with and without adjustments for spontaneous stone passage, medication noncompliance, or adverse events leading to patient withdrawal. Data were analysed using random‐effects meta‐analysis and meta‐regression. Certainty of evidence was assessed using the GRADE criteria. Results Among 15 randomised trials with 1653 patients, URS was effective and safe with a stone‐free rate of 81.2% and rare (2.3%) serious complications. The addition of preoperative alpha‐blockers reduced the need for ureteral dilatation (risk ratio [RR] = 0.48; 95% CI = 0.30 to 0.75; p = 0.002), access failure rate (RR = 0.36; 95% CI = 0.23 to 0.57; p

Objective: To evaluate efficacy and safety of either or both silodosin and mirabegron as MET for distal ureteric stones ≤ 10 mm. Patients and methods: This study enrolled a total of 105 patients, aged between 20 and 56 years, diagnosed by single radiopaque distal ureteral stone measuring ≤ 10 mm. The recruitment period spanned from May 2020 to December 2021. The patients were randomly divided into three groups, with each group consisting of 35 participants. Group A received a once-daily dose of 8 mg of silodosin, group B received a once-daily dose of 50 mg of mirabegron, and group C received a combination of both medications. Treatment was administered to all patients until the stone was expelled or for a maximum duration of four weeks. The stone-free rate was determined by analyzing KUB films with or without ultrasonography. Results: The rate of stone expulsion was significantly higher in group C compared to groups A and B (P = 0.04 and P = 0.004, respectively). The mean (standard deviation) time for stone expulsion in groups A, B, and C was 14 ± 2.3 days, 11 ± 3.1 days, and 7 ± 2.2 days, respectively. Group C demonstrated a significantly shorter stone expulsion time compared to groups A and B (P = 0.001 and P = 0.04, respectively). The frequency of renal colic in group C was significantly lower than that in groups A and B, resulting in a reduced requirement for analgesics (P < 0.05). Anejaculation occurred at a significantly higher rate in the silodosin group (73.9%) and combination group (84%) compared to the mirabegron group (P < 0.05). Conclusions: The findings of this study suggest that both silodosin and mirabegron are effective treatments for the expulsion of lower ureteric stones. Furthermore, the combination of these medications leads to an increased rate of stone expulsion and a reduced duration of expulsion. [ABSTRACT FROM AUTHOR]

Introduction In this study we aimed to compare the efficacy of mirabegron and silodosin as medical expulsive therapy (MET) for distal ureteric calculus ≤10 mm. Material and methods A total of 114 patients who met the inclusion criteria were prospectively randomised into 2 groups, 58 patients in the silodosin group and 56 patients in the mirabegron group. The drugs were given for a maximum of 4 weeks. The primary endpoint was the stone expulsion rate, and secondary endpoints were stone expulsion time and number of pain episodes. Results There were no statistically significant differences between the two groups in terms of mean age, gender, mean stone size, side, or hydronephrosis. Both groups exhibited similar rates of stone expulsion and expulsion time. Regarding pain management, the frequency of renal colic episodes was significantly lower with mirabegron compared to silodosin (2.3 ±0.2 vs 1.9 ±0.2, P <0.0001). Six patients were excluded from the study due to adverse drug reactions: 4 (6.15%) in the silodosin group (retrograde ejaculation, hypotension) and 2 (3.27%) in the mirabegron group (hypertension). Conclusions In among patients with distal ureteric stones measuring 5–10 mm, mirabegron did not demonstrate superiority in stone expulsion rate or expulsion time compared to silodosin. However, mirabegron significantly reduced the frequency of renal colic episodes. Therefore, mirabegron may be considered a preferable option for medical expulsive therapy for distal ureter stones over silodosin. [ABSTRACT FROM AUTHOR]

The current research developed a high‐performance thin layer chromatographic method based on green analytical chemistry and integrated experimental approaches of analytical quality by design for simultaneous estimation of solifenacin succinate and silodosin. The integration was planned to reduce energy and solvent usage, maximize efficacy, and minimize any negative environmental effects. Taguchi design for screening and optimization a Box–Behnken design was used. The n‐butanol:ethanol:triethylamine (6:4:0.1, v/v/v) mobile phase and ultraviolet detection at 221 nm were used to develop the method. As per International Council for Harmonization Q2(R1) specifications, the method was validated. Rf value for solifenacin succinate and silodosin was found to be 0.29 ± 0.02 and 0.58 ± 0.02 respectively. For solifenacin succinate and silodosin, the linearity was found over the concentration ranges of 500–2500 ng/band and 800–4000 ng/band. For solifenacin succinate, the limits of detection and quantification were found to be 13.00 and 39.34 ng/band, respectively, while for silodosin, they were 33.29 and 100.86 ng/band, respectively. For solifenacin succinate, the method revealed a percent recovery ranging from 98.49% to 99.50%, while for silodosin, it exhibited a range from 98.86% to 99.79%. The tools predicted greenness score to be 63 and 0.78, respectively, indicating the proposed method to be green. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether preoperative administration of silodosin can facilitate the placement of ureteral access sheath (UAS) prior to flexible ureteroscopy (F-URS) and reduce the occurrence of ureteric injury in challenging cases. Methods: This prospective randomized clinical trial was carried out on 147 patients diagnosed with upper ureteric stone or stone kidney, non-stented. The patients were randomly divided into two equal groups. Group A (silodosin group) included patients in whom F-URS was done with daily preoperative intake of 8 mg silodosin for 1 week and group B (placebo/control group) included patients in whom F-URS was done with daily preoperative intake of placebo tablets. Results: In group A, a total of 23 (33.3%) experienced ureteral wall injury following UAS insertion, while in group B, this occurred in 40 patients (59.7%). There was a statistically significant difference in the grade of ureteral wall injury between the two groups (P < 0.001). In the multiple regression analysis, age, operative time and silodosin were found to be significant risk factors for ureteral wall injury (P = 0.007, 0.041 and < 0.001, respectively). Conclusions: The administration of silodosin prior to retrograde intrarenal surgery (RIRS) effectively prevented significant ureteral wall damage and reduced initial postoperative discomfort. [ABSTRACT FROM AUTHOR]

Background: To study the impact of early in comparison to late catheter removal following acute urine retention (AUR) secondary to benign prostatic hyperplasia (BPH) using silodosin therapy on the outcome of trial without catheter (TWOC). Methods: Two hundred sixty patients with AUR 2ry to BPH were catheterized then were randomly divided to receive silodosin 8 mg either for three or 7 days followed by catheter removal and successful voiding unaided was assessed. Results: Out of the 260 men (mean age 64.8 ± 6.5 years) treated, 74 men who were receiving 3 days of silodosin and 88 patients who were receiving 7 days of silodosin didn't require re-catheterization on the day of TWOC (57% and 68% respectively, p = 0.096). Complications like urinary leakage, acute urinary tract infection, hematuria, or catheter blockage recorded in 21 men (16.2%) who received 3 days of silodosin, and in 63 men (48.5%) who received 7 days of silodosin (p ⩽ 0.001). Conclusion: Patients catheterized after AUR 2ry to BPH can spontaneously void following catheter removal if treated by silodosin, independent of the catheterization duration, while side effects have increased with prolonged catheterization. [ABSTRACT FROM AUTHOR]

Background: The existence of β3 receptors in the bladder and ureter was documented in many studies on animals and humans, it was documented that relaxation of the lower ureteral segment is achieved by the stimulation of these receptors. Our aim was to assess the efficacy and safety of mirabegron as a medical expulsive therapy (MET) for distal ureteral stones in comparison with silodosin and placebo. Methods: One hundred eighty patients with distal ureteral stone of 5–10 mm size were included in our study. They were divided into three groups, and each one consisted of 60 patients. Group I was given silodosin 8 mg, group II mirabegron 50 mg and group III placebo once daily. The treatment was prescribed for all the cases till stone expulsion or a maximum duration of 4 weeks. Primary outcome was the stone expulsion rate (SER). While secondary outcomes were stone expulsion time, side effects of the used drugs, hospital visits number for pain, and amount of analgesic taken. Results: We found that the SER was significantly higher in silodosin than mirabegron and placebo groups (61%, 38.6%, and 36.7%, respectively) (p = 0.013). Also, the stone expulsion interval was significantly shorter in silodosin than mirabegron and control groups (p < 0.001). While hospital visits number for pain, and amount of analgesic taken were comparable. There was no difference between the studied medications in terms of the adverse effects except for retrograde ejaculation (silodosin = 63.3%, mirabegron = 0%, and placebo = 0%; p < 0.001). Conclusion: Mirabegron has no medical expulsive effect. While silodosin improves SER and stone expulsion time. However, retrograde ejaculation was its main side effect and occurred in 63.3% of the male patients. Therefore, more research is needed to discover a more tolerable MET. [ABSTRACT FROM AUTHOR]

Background: Men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH), will have deterioration in the quality of life. Objective: The aim of this study was to evaluate the effect of combining pelvic floor muscle training with the urgency suppression technique (PFMT-st) and silodosin in comparison with silodosin in men with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) after 12 weeks of treatment. Patients and methods: A total of 158 patients were randomized into two groups. The control group received oral silodosin at a daily dose of 8 mg. The experimental group was administered PFMT-st and silodosin. The evaluation methods included the number of voids and intensity of urgencies over 24 h using a micturition diary, the International Prostate Symptom Score (IPSS), the Overactive Bladder Questionnaire (OAB-q), and the patient global impression of improvement (PGI-I). Results: 142 of 172 (86.6%) men were assessed (70 in the control group, 72 in the experimental group). The significant changes were in favor of the experimental group (p < 0.001) in the number of voids per 24 h (− 1.95 ± 1.94 vs. − 0.90 ± 1.44), the OAB-q symptom score (− 14.25 ± 10.05 vs. − 9.28 ± 10.60), the intensity of urgencies (− 0.97 ± 0.53 vs. 0.24 ± 0.57), the IPSS (− 4.59 ± 3.00 vs. − 2.30 ± 3.63), and in the PGI-I (2.24 ± 0.79 vs. 3.60 ± 0.92). Conclusions: The addition of PFMT-st to silodosin treatment significantly improved OAB in men with BPH. This is the first study to confirm that PFMT-st should be the first-choice treatment for OAB in BPH. [ABSTRACT FROM AUTHOR]

Purpose: The present paper takes a different and more critical look at the role of alpha-blockers, sometimes nicknamed as “magical pills”, in particular for stone disease and medical expulsive therapy (MET). Methods: A non-systematic narrative review was performed, synthesizing pertinent information from selected articles, and critically evaluating their conclusions. Sometimes different views on alpha-blockers were laid bare, including curiosities or other entertaining nuances suitable to the present topic, but always maintaining sharp objectivity and the foremost scientific rigor. Results and Conclusions: Alpha-blockers seem to be a panacea, being used to treat a wide variety of non-urological diseases and conditions. Urological applications include erectile dysfunction to benign prostatic hyperplasia, from incontinence to urinary retention, or even to facilitate urinary stone passage along the urinary tract. Due to its versatility, alpha-blockers appear to be the Swiss army knife of urological medications. However, the efficacy of alpha-blockers for MET, pain management, or facilitating upper tract access is very disappointing, bringing no, or in some instances, only marginal benefits. Their treatment results are far from being significant or impressive let alone magical. Regular sexual intercourse is an effective alternative to alpha-blockers, providing faster ureteral stone expulsion rates and reducing the need for pain medication. Most of the research supporting alpha-blockers has been based on single-center, underpowered, low-quality studies. These low-quality studies biased several subsequent meta-analyses, contaminating them with their low-quality data, enhancing and prolonging this delusion. These results emphasize the need for large, multi-centric, unbiased, randomized, double-blinded, placebo-controlled trials to prevent future year-long delusions that may afflict any medical field. [ABSTRACT FROM AUTHOR]

Background: Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration., Materials and Methods: The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41m/z values with significant differences between the drug-treated and control groups (p <0.01 and fold analysis≥1.5)., Results: According to multivariate data analysis, 17-β-estradiol, taurocholic acid, L-kynurenine, N-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5'-methylthioadenosine, L-methionine and S-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways., Conclusions: The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: This work aims to determine the efficacy and safety of preoperative alpha-blocker therapy on ureteroscopy (URS) outcomes., Methods: In this systematic review and meta-analysis of randomised trials of URS with or without preoperative alpha-blocker therapy, outcomes included the need for ureteral dilatation, stone access failure, procedure time, residual stone rate, hospital stay, and complications. Residual stone rates were reported with and without adjustments for spontaneous stone passage, medication noncompliance, or adverse events leading to patient withdrawal. Data were analysed using random-effects meta-analysis and meta-regression. Certainty of evidence was assessed using the GRADE criteria., Results: Among 15 randomised trials with 1653 patients, URS was effective and safe with a stone-free rate of 81.2% and rare (2.3%) serious complications. The addition of preoperative alpha-blockers reduced the need for ureteral dilatation (risk ratio [RR] = 0.48; 95% CI = 0.30 to 0.75; p  = 0.002), access failure rate (RR = 0.36; 95% CI = 0.23 to 0.57; p  < 0.001), procedure time (mean difference [MD] = -6 min; 95% CI = -8 to -3; p  < 0.001), risk of residual stone in the primary (RR = 0.44; 95% CI = 0.33 to 0.66; p  < 0.001) and adjusted (RR = 0.52; 95% CI = 0.40 to 0.68; p  < 0.001) analyses, hospital stay (MD = -0.3 days; 95% CI = -0.4 to -0.1; p  < 0.001), and complication rate (RR = 0.46; 95% CI = 0.35 to 0.59; p  < 0.001). Alpha-blockers increased ejaculatory dysfunction risk and were less effective for renal/proximal ureter stones. The certainty of evidence was high or moderate for all outcomes. The main limitation of the review was inconsistency in residual stone assessment methods., Conclusion: While URS is an effective and safe treatment for stone disease, preoperative alpha-blocker therapy is well tolerated and can further improve patient outcomes., Competing Interests: Drs. Bhojani, Chew, and Krambeck report consultancy with Boston Scientific (unrelated to the current study). Dr. Bhattacharyya reports employment with Boston Scientific. Dr. Ghani reports consultancy with Boston Scientific (unrelated to the current study) and investigator funding from Olympus, Storz, Ambu, and Coloplast. Dr. Miller reports consultancy with Boston Scientific (related to the current study)., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

The antiproliferative properties of metformin and silodosin have been observed in prostate cancer. Furthermore, it is hypothesized that the molecular pathways related to these drugs may impact the levels of human telomerase reverse transcriptase (hTERT) in prostate cancer cells. The aim of this study was to assess the effect of metformin and silodosin on the levels of hTERT in metastatic castration-resistant prostate cancer (mCRPC) cells. The present study employed an experimental design with a post-test-only control group. This study utilized the PC3 cell line as a model for mCRPC. A viability experiment was conducted using the CCK-8 method to determine the inhibitory concentration (IC50) values of metformin, silodosin, and abiraterone acetate (AA) after a 72-hour incubation period of PC3 cells. In order to investigate the levels of hTERT, PC3 cells were divided into two control groups: a negative control and a standard therapy with AA. Additionally, three experimental combination groups were added: metformin with AA; silodosin with AA; and metformin, silodosin and AA. The level of hTERT was measured using sandwich ELISA technique. The difference in hTERT levels was assessed using ANOVA followed by a post hoc test. The IC 50 values for metformin, silodosin, and AA were 17.7 mM, 44.162 mM, and 66.9 μM, respectively. Our data indicated that the combination of metformin with AA and the combination of metformin, silodosin and AA decreased the hTERT levels when compared to control, AA, and silodosin with AA. The administration of metformin resulted in a reduction of hTERT levels in the PC3 cell line, but the impact of silodosin on hTERT levels was not statistically significant compared to AA group., Competing Interests: Authors have no conflict of interest., (© 2024 by the authors.)

[Display omitted] • Novel co-formulation of silodosin and solifenacin for benign prostatic hyperplasia syndrome. • Smart spectrophotometric methods to overcome inherited spectral challenges. • Induction of mathematical filtration through computing one or more numerical values. • Greenness profile assessment via GSST, ComplexGAPI and AGREE as new metrics. • Good stickness of the proposed methods to the recent postulates of white analytical chemistry. Benign prostatic hyperplasia is one of the most predominant health disorders in men with increasing incidence by age and usually accompanied with other bothersome symptoms. A new fixed dose combination, containing Silodosin and Solifenacin, has been recently launched for relieving such disorder associated with overactive bladder syndrome. In the current work, three smart, innovative and white spectrophotometric methods have been newly developed and optimized for simultaneous determination of the studied drugs in their binary mixture using water as an eco-friendly solvent. The adopted strategy relied on calculation of one or two factors as numerical constant or spectrum allowing mathematical filtration of desired analyte and full removal of any overlapped components in the mixture. The developed methods are categorized over two spectrophotometric platform windows. Window I deals with absorption spectra in its native forms (zero-order) including a newly developed method termed induced concentration subtraction (ICS) as well as induced dual wavelength (IDW) methods. Whereas window III is concerned with ratio spectra as in induced amplitude modulation (IAM) method. Compared to classical spectrophotometric methods, the proposed ones are superior in overcoming the inherited challenges in zero-order absorption spectrum of Solifenacin, particularly its very low absorptivity and lack of unique absorption maximum. Validity of the methods were thoroughly assured as per ICH guidelines with unified regression over 3.0–50.0 µg/mL in ICS method while IDW and IAM ones possessed linearity ranges of 3.0–50.0 µg/mL of Silodosin and 5.0–60.0 µg/mL of Solifenacin. The work was also extended to verify content uniformity of dosage units in accordance with USP recommendations. Greenness profile of the proposed methods was clearly assessed, in comparison to the reported analysis ones, via state-of-the-art software metrics, namely , green solvent selection tool (GSST), complementary green analytical procedure index (ComplexGAPI) and analytical greenness (AGREE). Finally, the proposed methods were in good adherence to the recently published postulates of white analytical chemistry. [ABSTRACT FROM AUTHOR]

The study focuses to validate and develop a precise, simple and accurate stability indicating RP-HPLC method for estimation simultaneously of and silodosin and mirabegron in synthetic mixture. The chromatographic separation was achieved by using Shimpack Solar C 18 column (250×4.5mm, 5μm) with acetonitrile: 5mM ammonium acetate in ratio of 90:10% v/v as a mobile phase at a constant flow rate of about 1.2mL/min. The development and validation were carried out at detection wavelength of 229nm. We developed a robust RP-HPLC method, validated for linearity, precision, accuracy, specificity, and system suitability. The method demonstrated excellent linearity with correlation coefficient value r 2 was nearly 0.998 with linearity range 8-18μg/mL for Silodosin and 24-54μg/mL for mirabegron. LOD and LOQ were found to be lower; hence, the method is sensitive. Percentage recovery was obtained 99.97% and 99.99% for silodosin and mirabegron, respectively. In case of precision, robustness and repeatability, RSD was found to be less than 2. The validated and developed RP-HPLC method offers an efficient and practical approach for the simultaneous quantification of silodosin and mirabegron in pharmaceutical formulations, making it a valuable tool for quality control and pharmaceutical research., (Copyright © 2023 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)