Predictors of non-persistence in women with overactive bladder syndrome.

Persistence is important for the success in the treatment of women with overactive bladder syndrome (OAB). We aimed to identify the predictors of non-persistence in women with OAB after first-line medical treatment. All consecutive women with OAB (n = 608), who underwent urodynamic studies and received first-line medical treatment (5 mg of solifenacin or 25 mg of mirabegron per day) in a referral medical center, were reviewed. Mirabegron (hazard ratio [HR] = 0.711) was associated with a higher persistence rate, compared to solifenacin. Mirabegron treatment (HR = 0.269) was less likely to switch medication; however, a high Urogenital Distress Inventory score (HR = 1.082) was more likely to switch medication. Furthermore, old age (HR = 1.050, especially for ≥ 75 years) and high voided volume (dL, HR = 1.420, especially for voided volume ≥ 250 ml) were associated with added medication at follow-up. Additionally, women with low parity (HR = 0.653, especially for parity ≤ 3) and a low Incontinence Impact Questionnaire (IIQ-7) score (HR = 0.828, especially for IIQ-7 score ≤ 7) were associated with improvement without medication. In conclusion, mirabegron can be considered as the first frontline treatment to increase the persistence rate and decrease the rate of switched medications, compared to solifenacin. In addition, combination therapy or higher-dose monotherapy could be used as the first front-line treatment for women ≥ 75 years of age or with ≥ 250 ml of voided volume.

Separation and simultaneous estimation of enantiomers and Diastereomers of muscarinic receptor antagonist Solifenacin using stability-indicating Normal-phase HPLC technique with chiral stationary phase amylose tris-(3,5-dimethylphenylcarbamate).

The R,S-enantiomer impurity and diastereomer impurities (S,S-isomer and R,R-isomer) of the solifenacin (S,R-enantiomer) were effectively separated and quantified simultaneously utilizing normal-phase high-performance liquid chromatography with a chiral stationary phase consisting of amylose tris (3,5-dimethylphenylcarbamate) coated on silica-gel (Chiralpak, AD-H). The enantiomeric and stereo-selective separation was achieved within a run time of 35 minutes using a mobile phase of 'n-hexane, ethanol, and diethylamine' in an isocratic elution mode with a detection wavelength of 220 nm. The validation attributes assessed were accuracy (which showed excellent recoveries between 97.5% and 100.4%) and linearity (which was proven in the range of 0.081-1.275 µg.mL-1 , with a linear regression of 0.999). The stress testing experiments proved that the developed methodology by the HPLC technique has stability-indicating characteristics, as all closely eluting peak pairs were separated well with a resolution of 2.3 and without any interference. The proposed methodology was highly efficient in separating and simultaneously determining the chiral impurities (enantiomers and diastereomers) of the solifenacin in the release and stability sample analyses of drug substances and tablets in pharmaceutical formulations.

Novel Bioequivalent Tablet of Solifenacin Succinate Prepared Using Direct Compression Technique for Improved Chemical Stability.

We designed a bioequivalent tablet form of solifenacin succinate (SOL) with an improved storage stability using a direct compression (DC) technique. An optimal direct compressed tablet (DCT) containing an active substance (10 mg), lactose monohydrate, and silicified microcrystalline cellulose as diluents, crospovidone as a disintegrant, and hydrophilic fumed silica as an anti-coning agent was constructed by evaluating the drug content uniformity, mechanical properties, and in vitro dissolution. The physicochemical and mechanical properties of the DCT were as follows: drug content 100.1 ± 0.7%, disintegration time of 6.7 min, over 95% release within 30 min in dissolution media (pH 1.2, 4.0, 6.8, and distilled water), hardness > 107.8 N, and friability ~0.11%. The SOL-loaded tablet fabricated via DC showed an improved stability at 40 °C and RH 75%, exhibiting markedly reduced degradation products compared to those fabricated using ethanol or water-based wet granulation or a marketed product (Vesicare®, Astellas Pharma). Moreover, in a bioequivalence study in healthy subjects (n = 24), the optimized DCT offered a pharmacokinetic profile comparable to that of the marketed product, with no statistical differences in the pharmacokinetic parameters. The 90% CIs for the geometric mean ratios of the test to the reference formulation for the area under the curve and the maximum drug concentration in plasma were 0.98-1.05 and 0.98-1.07, respectively, and satisfied the FDA regulatory criteria for bioequivalence. Thus, we conclude that DCT is a beneficial oral dosage form of SOL with an improved chemical stability.

Micellar-enhanced and green-assessed first-derivative synchronous spectrofluorimetric approach for concurrent determination of alfuzosin hydrochloride and solifenacin succinate in different matrices: Docking simulation.

Alfuzosin hydrochloride (AZH) is co-formulated with solifenacin succinate (SOS) in Solitral® capsules for treating prostate hyperplasia in patients with overactive bladder syndrome. Herein and for the first time, an ultrasensitive synchronous spectrofluorimetric approach coupled with first-order derivative signal processing was designed for simultaneous determination of AZH and SOS in their pure forms, newly-released pharmaceutical capsules, and human biological fluids. AZH and SOS showed their conventional emission spectra in bi-distilled water at 382 nm and 294 nm after excitation at 325 nm and 250 nm, respectively. The native fluorescence intensities of AZH and SOS were greatly enhanced through micellar formation using sodium dodecyl sulfate surfactant (2%). The proposed approach included the use of synchronous mode at Δλ of 60 nm where the overlap between the studied analytes' fluorescence spectra wasn't completely resolved. The complete resolution was achieved by derivatization of the synchronized spectra to the first-order yielding two zero-crossing points which allowed the determination of AZH and SOS simultaneously without interference at 408 nm and 321 nm, respectively. Under optimum experimental circumstances, good linearities were accomplished over the concentration ranges of (1-24) ng/mL and (4-250) ng/mL with LOD of 0.26 ng/mL and 1.31 ng/mL for AZH and SOS, respectively. The proposed approach was validated successfully according to guidelines adopted by the ICH and compared statistically with the reported LC method with no discernible differences concerning accuracy or precision at p = 0.05. Successful application of the proposed approach achieved with excellent recovery percentages for analysis of the studied analytes in different matrices (pharmaceutical capsules and biological fluids) confirms its suitability for use in QC laboratories and other bioanalytical applications. The proposed approach's greenness was evaluated using two tools namely; penalty points scoring system and green analytical procedure index (GAPI) divulging excellent greenness of this approach relative to the reported LC method. The proposed approach relied chiefly on water as the cheapest and greenest solvent.

Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder.

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

Surgical Effect Observation and Treatment Strategy Analysis of Pseudo Urgency Syndrome.

Background and Objectives: pseudo urgency syndrome among patients with mixed incontinence (MUI) causes and the corresponding treatment strategies is explored. Materials and Methods: A total of 40 patients with MUI are treated with transobturator tape (TOT) and/or solifenacin succinate. Further, 30 patients with simple stress urinary incontinence (SUI) that were treated with transobturator tape (TOT) from the period of December 2018 to August 2020 are retrospectively analyzed; then, their clinical characteristics and therapeutic effects were summarized and analyzed. Results: The effective rates of SUI symptoms in MUI and simple SUI groups were 85% and 90%, respectively; further, the difference was noted as not statistically significant (P > 0.05). Among the 40 patients with MUI, 12 patients had unstable bladder contraction, and the other 28 patients showed normal bladder compliance. The treatment effectiveness rates of SUI symptoms in patients with unstable bladder contraction and normal bladder compliance were 83.3% and 85.7%, respectively; further, no significant difference was noted (P > 0.05). However, the effective rates of urge urinary incontinence (UUI) were 50% and 85.7%, respectively, however the difference was noted as statistically significant (P < 0.05). Conclusions: Most of the UUI symptoms in MUI patients may be "pseudo urgency syndrome" caused by the worry about the leakage of urine, rather than a real sense of UUI that is caused by excessive bladder excitement. Direct surgical treatment in patients with MUI can improve the symptoms of urinary incontinence, and the effect is more obvious in patients with urinary frequency who have normal bladder compliance according to urodynamics.

Metabolomics approach: Interpretation of changes in rat plasma metabolites after solifenacin treatment

Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate

The effects of pregabalin, solifenacin and their combination therapy on ureteral double-J stent-related symptoms: A randomized controlled clinical trial

ABSTRACT Background: Many medical therapies have been tested to deal with urinary stent-related symptoms (USRS). Several preventive and pharmaceutical methods have been already used for better compatibility of stents. However, the existing evidence for pharmacological treatment is still controversial. This study aims to evaluate the effects of pregabalin, solifenacin, and combination therapy on ureteral double-J stent-related symptoms following ureteroscopy and transureteral lithotripsy (TUL). Materials and methods: In a randomized controlled clinical trial, from November 2017 to March 2019, 256 patients who underwent ureteroscopy were enrolled. Patients were randomly divided into four groups including: group A received pregabalin 75mg BID (twice daily), group B received solifenacin 5mg orally once daily, group C received combination of pregabalin and solifenacin and the group D (control) given no drugs. Results: One hundred and fifty-one (58.9%) males and 101 (41.1%) females were enrolled in this study with a mean age of 43.47±7 (p=0.32, p=0.67). USSQ domains score such as urinary symptoms, pain, general condition, work performance, sexual matters and additional problems were significantly differenced during second and fourth week of follow-up among study groups (p <0.0001). In Tukey's multiple comparison test, urinary symptoms (p=0.735), pain (p=0.954) and sexual matters (p=0.080) in second week and work performance in forth week in group B was not significantly better than group D. Only group C in all indexes of USSQ showed significantly beneficial effects over group D (p <0.0001). Conclusion: Combination therapy of pregabalin and solifenacin has a significant effect on stent-related symptoms and is preferred over monotherapy of the respected medications.

The effects of pregabalin, solifenacin and their combination therapy on ureteral double-J stent-related symptoms: A randomized controlled clinical trial.

BACKGROUND: Many medical therapies have been tested to deal with urinary stent-related symptoms (USRS). Several preventive and pharmaceutical methods have been already used for better compatibility of stents. However, the existing evidence for pharmacological treatment is still controversial. This study aims to evaluate the effects of pregabalin, solifenacin, and combination therapy on ureteral double-J stent-related symptoms following ureteroscopy and transureteral lithotripsy (TUL). MATERIALS AND METHODS: In a randomized controlled clinical trial, from November 2017 to March 2019, 256 patients who underwent ureteroscopy were enrolled. Patients were randomly divided into four groups including: group A received pregabalin 75mg BID (twice daily), group B received solifenacin 5mg orally once daily, group C received combination of pregabalin and solifenacin and the group D (control) given no drugs. RESULTS: One hundred and fifty-one (58.9%) males and 101 (41.1%) females were enrolled in this study with a mean age of 43.47±7 (p=0.32, p=0.67). USSQ domains score such as urinary symptoms, pain, general condition, work performance, sexual matters and additional problems were significantly differenced during second and fourth week of follow-up among study groups (p <0.0001). In Tukey's multiple comparison test, urinary symptoms (p=0.735), pain (p=0.954) and sexual matters (p=0.080) in second week and work performance in forth week in group B was not significantly better than group D. Only group C in all indexes of USSQ showed significantly beneficial effects over group D (p <0.0001). CONCLUSION: Combination therapy of pregabalin and solifenacin has a significant effect on stent-related symptoms and is preferred over monotherapy of the respected medications.

A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial

ABSTRACT Introduction: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. Objectives: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. Patients and Methods: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. Results: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Conclusion: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial.

INTRODUCTION: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. OBJECTIVES: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. PATIENTS AND METHODS: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. RESULTS: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. CONCLUSION: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

The relation between the storage symptoms before and after transurethral resection of the prostate, analysis of the risk factors and the prevention of the symptoms with solifenacin

ABSTRACT Objective and Hypothesis We aimed to investigate the reasons of storage symptoms ( SS) after transurethral resection of the prostate (TURP). The hypothesis was that a positive correlation would be identified between preoperative and postoperative SS in patients with undergoing TURP and starting early solifenacin treatment in patients with high preoperative SS would be reasonable. In addition, we aimed to analyze multiple other risk factors for post-TURP SS. Materials and Methods A total of 160 patients undergoing TURP were prospectively evaluated and divided into two groups according to their OABS. Those with a score of ≥10 points were Group 1 (G1), and those with <10 points Group 2 (G2). In addition, patients in each group were randomly further divided into two subgroups: those who were started on 5 mg solifenacin succinate in the early postoperative period (G1/G2 A) and those who were not (G1/G2 B). In additions to SS Preop, perop and at the 3rd-month of postoperatively 14 variable were evaluated. The effects of these factors, surgery and the efficacy of an early medical treatment on the postoperative SS were investigated. LUTS were assessed by International Prostate Symptom Score (IPSS) and SS were assessed by sum of IPSS 2, 4 and 7 questionnaires (Storage, S- IPSS). Results Preoperative IPSS and S-IPSS were significantly higher in G1 (p<0.001); there was a significant improvement at IPSS, S-IPSS, QoL score, Qmax, and PVR for all groups after surgery. Only preoperative S-IPSS was found to have significant effect on postoperative SS (p<0.001). There was a significant difference between G1A and G1B but no significant difference between G2A and G2B in terms of SS at postoperatively. In addition to this, prostatic volume was found smaller than non-symptomatic patients in de novo SS patients. Conclusion TURP provides significant improvement in both storage and voiding symptoms. The predictive value of the preoperative S-IPSS on postop SS is significant. These results suggest that 5 mg solifenacin succinate treatment in the early postoperative period may be beneficial for patients with high preoperative SS and may not be beneficial in others. Small prostatic volume may bode ill for postoperative SS in the patients with de novo SS.

Evaluation of in Vitro and in Vivo Transdermal Absorption of Solifenacin Succinate.

Solifenacin (Sol), an antimuscarinic agent has been widely used for the treatment of overactive bladder. Transdermal formulations can be administered without water as well as absorbed slowly into the blood over a long period of time. The aim of this study was to develop cream and tape formulations of Sol, and evaluate the transdermal permeation and absorption of the drug from the two formulations in vitro and in vivo, respectively. In the preparation of cream formulation, Sol succinate was dissolved in purified water, and the mixture was added to the hydrophilic cream. Then, aqueous sodium hydroxide was added to the cream. In the tape formulation, Sol succinate was dissolved in a solvent with propylene glycol, diisopropanolamine, triethyl citrate, and EUDRAGIT E100. The dissolved solvent was poured onto a polyethylene film. Cream (5%) and tape (15%) formulations demonstrated high skin permeability. Addition of an adsorption enhancer (N-methyl-2-pyrrolidone) did not further increase the level of skin permeability. In subsequent in vivo experiments in rats, both the cream and tape formulations led to slow absorption of Sol into plasma, with increased t1/2 compared with oral administration. Plasma Sol concentrations peaked 24 h after transdermal application and the drug was still detectable in plasma 72 h after application. Additionally, the cream (5%) and tape (15%) formulations resulted in a higher area under the plasma concentration vs. time curve from 0 to 72 h (AUC0-72) compared with oral formulation (30 mg/kg). In conclusion, significant in vitro permeability and in vivo absorption of Sol from the transdermal formulations were observed.

Efficacy and tolerability of mirabegron in female patients with overactive bladder symptoms after surgical treatment for stress urinary incontinence

ABSTRACT Purpose To evaluate the efficacy and tolerability of mirabegron in females with overactive bladder (OAB) symptoms after surgical treatment for stress urinary incontinence (SUI). Materials and Methods The study was conducted with a prospective, randomized and double-blinded design. 62 patients over the age of 40 who met the inclusion-exclusion criterias of the study were enrolled and randomly divided into two groups as Group A (mirabegron 50mg) and B (solifenacin 5mg). Patients were compared based on efficacy of treatment [Patient Perception of Bladder Condition (PPBC) scale and micturition diaries], safety of treatment (heart rate, systolic and diastolic blood pressure, adverse events), number of micturitions per day, patient's satisfaction status after treatment [Visual Analog Scale(VAS)] and quality of life. Results The mean age of the population was 48.2±3.8 years and the duration of OAB symptoms was 5.9±2.9 months. Baseline values for the mean number of micturitions, volume voided in each micturition, nocturia episodes, urgency and urgency incontinence episodes were 15.3±0.34, 128±3.88mL, 3.96±1.67, 5.72±1.35 and 4.22±0.69, respectively. After treatment, values for these parameters were 11.7±0.29, 164.7±2.9mL, 2.25±0.6, 3.38±0.71, 2.31±0.49 respectively. Quality of life score, symptom bother score, VAS for treatment satisfaction score, PPBC score after treatment were 66.1±0.85, 43.7±0.77, 4.78±0.14, 4.78±0.14, respectively. There were no significant differences between two groups on any parameter. However, mirabegron showed better tolerability than solifenacin, particularly after 6 months. Conclusion Mirabegron is safe, effective and tolerable in the long-term treatment of females with OAB symptoms after surgery for stress urinary incontinence.

Effect of tadalafil add-on therapy in patients with persistant storage symptoms refractory to α1 -adrenoceptor antagonist monotherapy for benign prostatic hyperplasia: A randomized pilot trial comparing tadalafil and solifenacin.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α1 -adrenoceptor antagonists. METHODS: Patients with persistent storage symptoms refractory to α1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated. RESULTS: Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups. CONCLUSIONS: Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α1 -adrenoceptor antagonists.

Content Determination of 7 Related Substances in Solifenacin Succinate Raw Material by HPLC with Principal Component Self-control with Correction Factor / 中国药房

OBJECTIVE： To establish method for simultaneous determination of 7 related substances in solifenacin succinate raw material. METHODS： HPLC method was adopted. The determination was performed on Thermo Hypersil ODS C18 column with mobile phase consisted of 0.02 mol/L KH2PO4 （0.02％ triethylamine， pH＝3.0）-acetonitrile （gradient elution） at the flow rate of 1.2 mL/min. The detection wavelength was set at 210 nm， and column temperature was 40 ℃. The sample size was 20 μL. The regression equation of solifenacin succinate and impurity A， C， D， I， J， K， L were drawn. Correction factors of impurities to solifenacin succinate were calculated with slope. The contents of impurities A， C， D， I， J， K and L were determined in 3 batches of solifenacin succinate raw material. RESULTS： The linear ranges of impurity A， C， D， I， J， K and L were 0.148 1-0.740 3， 0.142 9-0.714 5， 0.141 1-0.705 6， 0.148 9-0.744 6， 0.152 0-0.759 9， 0.137 9-0.689 6， 0.020 0-0.100 0 μg/mL （r＝0.999 8， 0.999 9 or 1.000 0）， respectively. The relative correction factors were 0.51， 0.40， 0.41， 0.91， 0.47， 0.85， 1.23. The limits of detection were 0.049 3， 0.047 6， 0.047 0， 0.048 1， 0.050 7， 0.046 0， 0.006 7   μg/mL. The quantification limits were 0.148 1， 0.142 9， 0.141 1， 0.148 9， 0.152 0， 0.137 9， 0.020 0 μg/mL， respectively. RSDs of precision， stability （24 h） and reproducibility tests were all lower than 5.0％ （n＝6）. Average recoveries were 101.09％， 97.58％， 93.77％， 98.56％， 99.68％， 97.07％ and 93.54％； RSDs were 0.75％ ， 0.51％， 0.47％， 0.84％， 0.70％， 0.75％， 1.21％ （n＝9）. The contents of impurity I in 3 batches of solifenacin succinate raw material were 0.015％-0.018％， other impurities were not detected. CONCLUSIONS： The method is sensitive， accurate and reliable， which can be used to determine the related substances of solifenacin succinate raw material.

Efficacy of Additional Solifenacin Succinate Therapy for Storage Symptoms in Females with Uncomplicated Lower Urinary Tract Infection: The SOLUTION Randomized Controlled Trial.

BACKGROUND: urinary tract infection (UTI) is often treated in daily practice as overactive bladder (OAB) by giving anticholinergic, the recommended treatment options of OAB. However, anticholinergic application for UTI symptoms relief has never been investigated. To our knowledge, this study was the first randomized trial which investigate anticholinergic use for UTI treatment. This study aimed to evaluate whether additional anticholinergic is beneficial alongside an empiric antibiotic therapy in reducing symptoms and tolerable for females with uncomplicated UTI. METHODS: this was a randomized double-blind controlled trial that included female aged >18 y.o with uncomplicated lower UTI. Patients were randomly assigned to either solifenacin succinate 5 mg (group 1) or placebo (group 2) in addition to empiric levofloxacin 500 mg treatment for 3 days. Those with structural and/or functional abnormalities of the urinary tract and allergic reaction history were excluded. We observed changes in overactive bladder symptom score (OABSS), patient perception of bladder condition (PPBC) score, patient-reported symptoms and adverse events. RESULTS: a total of 126 patients, 63 for each group, initiated the trial with median age of 44 (19-67) y.o. There were no differences of age, OABSS, and PPBC score between the 2 groups at baseline. We found significant (p<0.05) reduction of OABSS and PPBC score in both groups at the end of therapy; however the amount of reduction were not different between groups. In group 1 we found 22.2% of patients complained of dry mouth and 25.4%, 4.7%, 3.2% of patients complained of nausea, somnolence and constipation respectively. In group 2 we found 20.0%, 21.7% and 3.3% patients who complained of dry mouth, nausea, and somnolence respectively. One patient in group 2 experienced allergic reaction and was dropped out. CONCLUSION: we found no significant difference in OABSS and PPBC score reduction by adding anticholinergic to antibiotic therapy for females with uncomplicated UTI. There was no serious adverse event recorded.

Clinical optimal dose of solifenacin succinate for nursing patients after transurethral resection of the prostate during the perioperative period.

Transurethral plasma kinetic resection is an efficient and safe surgery for the treatment of benign prostatic hyperplasia. Solifenacin succinate (SOL) is safe and clinically efficient for patients who endure transurethral resection of the prostate (TURP) during the perioperative period. The objective of this study was to evaluate the clinical optimal dose of SOL for nursing patients after TURP during the perioperative period. Patients were recruited and randomized into three groups: SOL (3 mg), SOL (6 mg), and SOL (10 mg). All patients received medical care for 3 weeks after TURP. Levels of inflammatory cytokines, including IL-6, epithelial neutrophil activation peptide-7 (ENA-7), tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-17 and IL-8, were investigated in the patients of all three groups. The efficacy of SOL was analyzed via the following scores: International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OBSS), short-form voiding (SFV) and storage score (TS) of International Continence Society (ICS). Outcomes showed that IL-2 and ENA-7 plasma concentration levels were upregulated, whereas TNF-α, IL-6, IL-17 and IL-8 were downregulated, in all three groups. The findings showed that patients that received SOL (6 mg) exhibited significant improvements compared to the other patient groups from baseline to the end of treatment, as determined by IPSS, OBSS, ICS, SFV, TS (P<0.01). In conclusion, these results indicate that SOL (6 mg) is the optimal dose for patients who undergo TURP during the perioperative period. Notably, treatment with SOL (6 mg) exhibited significant additional benefits in terms of lower urinary tract symptoms during the early recovery period after TURP, suggesting SOL is clinically significant for nursing patients who suffer have undergone TURP during the perioperative period.

Effectiveness and durability of solifenacin versus percutaneous tibial nerve stimulation versus their combination for the treatment of women with overactive bladder syndrome: a randomized controlled study with a follow-up of ten months

ABSTRACT Purpose To assess effectiveness and durability of Solifenacin (SS) versus tibial nerve stimulation (PTNS) versus combination therapy (PTNS + SS) in women with overactive bladder syndrome (OAB). Materials and Methods 105 women with OAB were divided randomly into three groups of 35 patients each. In group A women received SS, in group B women underwent PTNS, in group C women underwent combination of PTNS + SS. Improvements in OAB symptoms were assessed with OABSS questionnaire; patients' quality of life was assessed with OAB-q SF questionnaire. Evaluation of effectiveness of treatments was performed with PGI-I questionnaire. OABSS and PGI-I were also assessed monthly for ten months. Results All treatments were effective on symptoms. PTNS showed a greater effectiveness than SS, but PTNS + SS was more effective than SS and PTNS. Furthermore, PTNS + SS showed a greater duration of effectiveness than PTNS and SS. Conclusions Combination of PTNS with SS showed more effectiveness and more durability than PTNS and SS alone.

Effectiveness and durability of solifenacin versus percutaneous tibial nerve stimulation versus their combination for the treatment of women with overactive bladder syndrome: a randomized controlled study with a follow-up of ten months.

PURPOSE: To assess effectiveness and durability of Solifenacin (SS) versus tibial nerve stimulation (PTNS) versus combination therapy (PTNS + SS) in women with overactive bladder syndrome (OAB). MATERIALS AND METHODS: 105 women with OAB were divided randomly into three groups of 35 patients each. In group A women received SS, in group B women underwent PTNS, in group C women underwent combination of PTNS + SS. Improvements in OAB symptoms were assessed with OABSS questionnaire; patients' quality of life was assessed with OAB-q SF questionnaire. Evaluation of effectiveness of treatments was performed with PGI-I questionnaire. OABSS and PGI-I were also assessed monthly for ten months. RESULTS: All treatments were effective on symptoms. PTNS showed a greater effectiveness than SS, but PTNS + SS was more effective than SS and PTNS. Furthermore, PTNS + SS showed a greater duration of effectiveness than PTNS and SS. CONCLUSIONS: Combination of PTNS with SS showed more effectiveness and more durability than PTNS and SS alone.