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

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

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.

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.

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.

Effects of Sacral Nerve Root Magnetic Stimulation Combined with Solifenacin on Refractory Overactive Bladder in Women / 中国康复理论与实践

Objective:To investigate the clinical efficacy of sacral nerve root magnetic stimulation combined with Solifenacin in women with refractory overactive bladder (OAB). Methods:From January to December, 2017, 120 women with refractory OAB were randomly divided into sacral nerve root magnetic stimulation group (group A, n = 40), Solifenacin group (group B, n = 40), and combined treatment group (group C, n = 40). Before and after treatment, they were assessed with the urine diary (number of daily urination, number of nightly urination, single urine output, number of urgent urination), urodynamic index (initial urinary bladder capacity, maximum bladder capacity) and Overactive Bladder Symptom Score (OABSS). Results:Two patients from group A, one from group B and one from group C were dropped out. The number of daily urination, the number of nightly urination, the single urine output, the number of urgent urination, the initial urinary bladder capacity and maximum bladder capacity, and OABSS were better in group C than in groups A and B (P < 0.05). Conclusion:Sacral nerve root magnetic stimulation combined with Solifenacin is effective and better than anyone alone on women with refractory OAB.

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.

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.

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.

Pharmacokinetics comparison of solifenacin tartrate and solifenacin succinate: a randomized, open-label, single-dose, 2-way crossover study in healthy male volunteers

Solifenacin is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms. Solifenacin tartrate is a newly developed salt formulation of solifenacin. This study compared the pharmacokinetic and safety properties after single-dose administration of solifenacin tartrate (test formulation) and solifenacin succinate (reference formulation) in healthy male volunteers. A total of 36 subjects were enrolled in this randomized, open-label, single-dose, two-way crossover study. During each treatment period, subjects received the test formulation or reference formulation. Plasma samples were collected at pre-dose and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48 and 72 hours post-dose. Safety was assessed by adverse events, physical examinations, laboratory assessments, 12-lead electrocardiograms, and vital signs. Thirty-three subjects completed the study and were included in the pharmacokinetic analysis. The mean (standard deviation) values of AUC(last) for the test and reference formulations were 486.98 (138.47) and 469.07 (128.29) h·ng/mL, respectively. The mean (standard deviation) values of C(max) for the test and reference formulations were 14.66 (3.85) and 14.10 (3.37) ng/mL, respectively. The 90% confidence intervals for AUC(last) and C(max) were 0.9702 to 1.1097 and 0.9779 to 1.0993, respectively. All adverse events were mild or moderate, and there were no serious adverse events. The pharmacokinetic properties of solifenacin tartrate were similar to those of solifenacin succinate and met the acceptance criteria for bioequivalence. Both formulations were safe, and no significant difference was observed in the safety assessments of the formulations.

Comparison of Solifenacin and Trospium in Treatment of Overactive Bladder / 医学研究杂志

Objective To compare the use of solifenacin and trospium in treatment of overactive bladder (OAB).Methods This prospective study was conducted on patients diagnosed with OAB who presenting to the Department of urology,Changzhou No.3 People's Hospital between March 2015 and May 2016.Patients were randomized into 2 groups.Group A (n =40) received 5 mg solifenacin once daily,while Group B (n =39) received 20 mg trospium twice daily.All the patients' OAB symptom scores (OABSS) in weeks 0,4,and 12 were recorded.In addition,side effects of the drugs were evaluated.Results Average OABSS was determined as:9.3 ± 2.6 (Group A) and 10.2±1.9 (Group B) at week0;2.5±1.3 (GroupA) and 2.7±1.4 (Group B) at week4;and 1.4±0.5 (Group A) and 1.3 ± 0.6 (Group B) at week 12.In addition,no statistically significant difference was found between the scores (P =0.084,P =0.512 and P =0.423).The discontinuation rate of medication due to its side effects was 0 (0％) for Group A,and 5 (12.8％) for Group B.Intragroup changes in the scores 0 weeks-4 weeks,0 weeks-12 weeks and 4 weeks-12 weeks values was statistically significant in both groups (P =0.000).Conclusion No significant difference was found between the OABSS of these 2 drugs.However,discontinuation of drugs due to side effects was more frequent in trospium.

Evaluation of combination therapy with α and M receptors antagonist for the treatment of double J stents related lower urinary tract symptoms / 中国综合临床

Objective To evaluate the efficacy of combination therapy with α and M receptors antagonist for the treatment of double J stents related lower urinary tract symptoms.Methods From January 2013 to December 2016,one hundred and twenty patients were accepted the doubte J stents indwelling after the ureteral lithotripsy,laparoseopie ureterlithotomy and pyeloureteroplasty.They were divided into four groups randomly,including control group(30 cases,no drugs were taken),tamsulosin group(30 cases,0.2 mg tamsulosin was taken qd),solifenacin group(30 cases,5 mg solifenacin was taken qd),combination group(30 cases,0.2 mg tamsulosin and 5 mg solifenacin were taken qd).The IPSS scores,QOL scores and visual analogue pain scale(VAPS)scores were assessed pre-operation,1 week after operation,and 4 weeks after operation, respectively.Results The total IPSS scores in the combination group 4 weeks after operation was(8.21±2.36) points,compared with the control group((13.68 ± 3.65)points),the tamsulosin group((12.59 ± 3.76) points),the solifenacin group((12.39 ±4.58)points),the difference was statistically significantly lower(F=7.905,P<0.05).And 4 weeks after operation,the QOL scores in the combination group((1.52±0.99)points) was significantly lower than that in the control group((2.86±1.14)points),the tamsulosin group((2.69± 1.21)points)and the solifenacin group((2.74 ± 1.40)points)(F=13.725,P<0.05).While the VAPS scores didn′t show significant differences among those groups(P>0.05).Conclusion α and M receptors antagonist combination therapy can significantly improve lower urinary tract symptom due to indwelling double J stents.

Effect of Solifenacin and Epalrestat combination therapy on type 2 diabetes complicated with overactive bladder / 中国糖尿病杂志

Objective To investigate the effect of solifenacin and epalrestat combination therapy on type 2 diabetes complicated with overactive bladder (OAB).Methods A total of 80 patients with T2DM and OAB were randomly divided into three groups:control group (Con group,n=24),epalrestat group (n=29),and solifenacin combines epalrestat group (n=27).Con group was treated with conventional therapy such as routine bladder training,anti-hyperglycemic,anti-hypertensive,lipid lowering treatment,and nerve nutrition.Epalrestat group was treated with epalrestat 50 mg,3/d orally on the basis of conventional treatment.Solifenacin group was treated with solifenacin 5 mg,1/d,and epalrestat 50 mg,3/d orally.All the subjects were followed up for 12 weeks.Voiding diary,OAB self rating scale (OABSS) score,maximum urinary flow rate (Qmax),average urinary flow rate (Qave),and urine volume(VV) were recorded.Results The daily micturition frequency in 24h,times of nocturia,urgency,frequency,and urinary incontinence,and OABSS scores were lower,while Qmax,Qave,and VV were higher in solifenacin group than in Con group and epalrestat group (P<0.05).The OABSS scores were lower while VV was higher in epalrestat group than in Con group (P<0.05).The total effective rate was higher in solifenacin group than in Con group and epalrestat group (92.6% vs 69% vs 41.7%,P<0.05).Conclusion Solifenacin and epalrestat combination therapy was effective in treating patients with T2DM and OAB.

Efficacy and safety of solifenacin in the treatment of patients with bladder spasm after transurethral resection of prostate:a systematic review and meta-analysis / 中国基层医药

Objective To systematically review the efficacy and safety of solifenacin in the treatment of patients with bladder spasm after transurethral resection of prostate based on current evidence.Methods We searched Pubmed,EMbase,the Cochrane Library,CBM,CNKI,VIP and Wanfang Database from the establishment to October 2016 for the published literature on the treatment of patients with bladder spasm after transurethral resection of prostate with solifenacin.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Then,meta-analysis was performed using RevMan 5.3 software.Results A total of 11 RCTs involving 621 patients were included.The results of meta-analysis showed that:compared with the no-solifenacin group(n=311),the numbers of bladder spasm episodes[MD=-1.38,95%CI(-1.97,-0.97)P<0.00001],duration of bladder spasm[MD=-0.26,95%CI(-0.41,-0.11),P=0.0008],the time of bladder perfusion clearance[MD=-0.59,95%CI(-0.88,-0.29),P<0.0001],indwelling catheter delivery[MD=-0.29,95%CI(-0.48,-0.11),P=0.09]in solifenacin group(n=310) reduced significantly,and there was no statistical difference in the incidence of overall adverse events between the two groups[RR=0.71,95%CI(0.17,2.98),P=0.64].Conclusion Current evidence indicates that solifenacin is more effective and safe in the treatment of patients with bladder spasm after transurethral resection of prostate.Due to the limited quantity and quality of the include studies,more high quality studies are needed to verify the above conclusion.

Efficacy of solifenacin in the prevention of cystospasm after radical prostatectomy / 中国医师进修杂志

Objective To study the efficacy and security of solifenacin in prevention of cystospasm after radical prostatectomy. Methods The clinical data of 93 localized prostate cancer patients who had underwent laparoscopic radical prostatectomy were retrospectively analyzed. The patients were divided into solifenacin group (52 cases) and control group (41 cases) based on the condition of taking solifenacin after operation. The day and night frequency and duration of cystospasm from the first day to the third day after operation, incidence of urine extravasation, duration of bloody urine, time of pelvic cavity drainage and ureter retention, untoward reaction (dry mouth, headache and abdominal distention) was compared between two groups. Results The day and night frequency and duration of cystospasm at second day and third day after operation in solifenacin group were significantly lower than those in control group. Day frequency of cystospasm: (1.54 ± 0.42) times vs. (3.35 ± 0.43) times and (1.38 ± 0.58) times vs. (2.86 ± 0.66) times, night frequency of cystospasm:(1.66 ± 0.63) times vs. (3.58 ± 0.72) times and (1.47 ± 0.33) times vs. (3.27 ± 0.68) times, duration of cystospasm:(0.18 ± 0.11) h vs. (0.33 ± 0.18) h and (0.21 ± 0.09) h vs. (0.29 ± 0.21) h, and the incidence of urine extravasation at the third day after operation in solifenacin group was significantly lower than that in control group: 1.92% (1/52) vs. 17.07% (7/41), and there were statistical differences (P0.05). Conclusions Solifenacin can reduce the frequency of cystospasm and shorten the duration of cystospasm effectively after radical prostatectomy. It has a positive effect on reducing the incidence of urinary extravasation and shorting the extubation time. It is helpful to improve the quality of life and the recovery of the patients.

Meta-Analysis of the Efficacy and Safety of Mirabegron Add-On Therapy to Solifenacin for Overactive Bladder / 대한배뇨장애요실금학회지

PURPOSE: We performed a meta-analysis to evaluate the efficacy and safety of mirabegron add-on therapy to solifenacin for patients with overactive bladder (OAB). METHODS: We conducted a systematic literature review to identify all randomized, double-blind, controlled trials (RCTs) of this combination (mirabegron and solifenacin) for OAB. Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched. A manual search was also performed to investigate relevant references from the retrieved studies. RESULTS: Four publications describing 5 RCTs that compared combination therapy with solifenacin, including a total of 3,309 patients, were analyzed. The mean number of micturitions per 24 hours (mean difference [MD], -0.45; 95% confidence interval [CI], -0.65 to -0.26; P < 0.00001), number of episodes of incontinence per 24 hours (MD, -0.71; 95% CI, -0.14 to -0.02; P=0.04), volume voided per micturition, and number of urgency episodes per 24 hours demonstrated that combination therapy was more effective than solifenacin therapy alone. Safety assessments, including common treatment-emergent adverse events (odds ratio, 1.09; 95% CI, 0.95–1.27; P=0.23) and discontinuations due to adverse events (P=0.30), demonstrated that the combination therapy was well tolerated. CONCLUSIONS: This meta-analysis suggests that mirabegron therapy as an add-on to solifenacin provides a satisfactory therapeutic effect for OAB symptoms with a low occurrence of side effects.

Influence of Daytime or Nighttime Dosing with Solifenacin for Overactive Bladder with Nocturia: Impact on Nocturia and Sleep Quality

We compared changes in nocturia and sleep-related parameters between daytime and nighttime solifenacin dosing in patents with overactive bladder (OAB) and nocturia. We comparatively analyzed the data of a 12-week prospective, open-label, multicenter, randomized study. All 127 patients who presented to 5 centers in Korea for the treatment of OAB with nocturia between January 2011 and December 2013 were enrolled in this study. The patients were divided into 2 groups by medication timing: group 1, daytime (n = 62); and group 2, nighttime (n = 65). The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Athens Insomnia Scale (AIS) were used to assess OAB symptoms and sleep quality. We evaluated the parameter changes before and 12 weeks after daytime or nighttime solifenacin administration. Baseline data, which included sex, age, body mass index (BMI), total AIS, IPSS, and OABSS, did not differ between the 2 groups. Total IPSS, OABSS, and total AIS significantly improved after solifenacin administration regardless of timing (P < 0.001). After solifenacin administration, the number of nocturia episodes decreased in the group 1 and 2 (P < 0.001). There were no significant intergroup differences in changes in AIS, IPSS, OABSS, and number of nocturia episodes 12 weeks after solifenacin administration. Treating OAB with solifenacin may improve nocturia and sleep quality, but advantages did not differ significantly by medication timing.

Curative effect of testosterone combined with solifenacin for patients with lower urinary tract symptoms in ;late-onset hypogonadism / 中国基层医药

Objective To investigate the clinical efficacy and safety of testosterone supplement and Mreceptor blockers in the treatment of patients with lower urinary tract symptoms(LUTS)in late -onset hypogonadism(LOH). Methods 28 cases diagnosed as LOH with mild to moderate LUTS were collected.They were given testosterone supplementation (oral testosterone undecanoate capsules,80mg,2 times/d)and M receptor blocker (oral succinate solifenacin tablet,5mg,1 time /d)treatment for 1 -3 months.After treatment for 1 month and 3 months respectively, reviewd PSA,serum total testosterone (TT),international prostate of urinary storage symptoms score (urinary storage IPSS),quality of life (QOL)score,international index of erectile function (IIEF -5)score,maximum urinary flow rate (Qmax),residual urine (Ru)and rectal examination (DRE).The improvement of LUTS before and after treatment was evaluated.Results 1 month after treatment,1 patient was difficult to tolerate the solifenacin side effects and took testosterone supplementation alone.The rest 27 patients were able to take medicine for 3 months.After 1 month and 3 months treatment,the IPSS score had significant differences compared with before treatment[(10.3 ±2.1)points vs (14.2 ±3.3)points and (9.42 ±1.8)points vs (14.2 ±3.3)points,t =13.67,14.72,all P <0.05 ].After 3 months treatment,the QOL and IIEF -5 scores were (2.1 ±0.7)points vs (4.3 ±0.6)points and (16.8 ± 3.6)points vs (11.9 ±2.5)points,Qmax was (12.5 ±5.6)mL/s vs (9.8 ±4.8)mL/s(t =6.42,5.64,14.92,all P <0.05 ),the difference was statistically significant compared with before treatment.There were no significant changes in PSA and RU before and after treatment.All patients had no severe complications such as acute urinary retention.Conclusion Combination of testosterone and testosterone in the treatment of LUTS patients in LOH is safe and effective,and can significantly improve the LUTS and quality of life.

Efficacy of solifenacin in the treatment of bladder spasm after surgical operation of chlidren hypospadias / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of solifenacin in the treatment of bladder spasm after surgical operation of chlidren hypospadias.Methods From January 2014 to May 2015,60 cases of children more than 4 years old after surgical operation of hypospadias who had symptom of bladder spasm on the day of surgery were assigned into the study group (n =30) and control group (n =30),based on simple randomization.On the first day,the frequency of spasm,the duration of spasm and the incidence of urine extravasation were recorded regarded as the first day condition of bladder spasm.Patients in the study group were treated with solifenacin (5 mg once daily) for a nine days period from l th day postoperation.Patients in the control group were not treated with solifenacin.The frequency of spasm,the duration of spasm and the incidence of urine extravasation of the two groups were recorded and compared on the 3th and 9th day.Adverse events with solifenacin of two groups were recorded.The function of liver and kidney in the study group were recorded and compared.Results There were statistically significant differences(P ＜0.01) in favor of the study group over the control group in the aspect of the frequency of spasm,the duration of spasm and the incidence of urine extravasation on the 3th and 9th day.In the study group,the data compared among l th,3th and 9th was statistically significantly different,opposite to the control group.There was no statistically significant difference between the liver and kidney function of preoperation and the 9th day in the study group.The frequency of adverse events between two groups had no statistically significant difference.Conclusions Solifenacin is effective and safe in the treatment of bladder spasm after surgical operation of chlidren hypospadias

Similarity Evaluation of Dissolution Profiles of Self-development and Original Preparation of Solifenacin Suc-cinate Tablet / 中国药房

OBJECTIVE:To explore the similarity of dissolution profiles of self-development and original preparation of Solife-nacin succinate tablet,and provide reference for the prescription and process screening of the former one and the quality similarity evaluation of the latter one. METHODS:The paddle method was adopted with rotational speed of 50 r/min,using water,pH1.2 hy-drochloric acid solution,pH4.0 acetate buffer solution and pH6.8 phosphate buffer solution as dissolution media,HPLC was used to determine the cumulative dissolution of main components of self-development and original preparation of Solifenacin succinate tablet at different time points,dissolution profile was drew,then f2 was used to evaluate its similarity. RESULTS:In the 4 dissolu-tion media,the f2 of both self-development and original preparation of Solifenacin succinate tablet was higher than 50,which indi-cated that the dissolution profiles showed similarity. CONCLUSIONS:The established HPLC is suitable for the dissolution determi-nation of Solifenacin succinate tablet;the dissolution profiles of the self-development and original preparations are basically simi-lar,which indicates the prescription and technology of self-development preparation are feasible.