Efficacy and Safety of Propiverine and Solifenacin for the Treatment of Female Patients with Overactive Bladder: A Crossover Study

Objectives: To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB). Methods: A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P‐S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S‐P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS). Results: A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P‐S and 44 in Group S‐P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P‐S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039). Conclusion: Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine.     

Clinical Impact of Solifenacin on Generic and Symptom‐Specific Quality of Life for Females with Overactive Bladder: Using the Overactive Bladder Symptom Score and Rand Medical Outcomes Study 36‐Item Health Survey

Objectives: We evaluated the effectiveness of antimuscarinic treatment on disease‐specific and generic quality of life (QoL) in females with clinically diagnosed overactive bladder (OAB) by prospectively analyzing improvements in the overactive bladder symptom score (OABSS) and the Rand Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36). Methods: We prospectively recruited newly diagnosed female patients with OAB. Pretreatment disease‐specific symptoms were documented, and generic QoL questionnaires were administered. All subjects received solifenacin 5 mg/day for >8 weeks. Symptoms and general health‐related QoL (HRQoL) were assessed using the OABSS and SF‐36, respectively. Other objective variables, such as maximum urinary flow rate and postvoid residual urine volume, were also evaluated. Results: Seventy‐eight subjects met all inclusion criteria and no exclusion criteria. After 8 weeks, the mean OABSS decreased by approximately 50% compared with baseline (from 9.1 ± 2.8 to 4.5 ± 3.6). All individual scores in OABSS improved after administration of solifenacin. Before treatment, the scores of the study subjects in all SF‐36 domains were significantly worse than the age‐ and gender‐adjusted Japanese national norms (P < 0.01), except the vitality (VT) scale. Intra‐group comparisons between age groups showed worse mental health (MH) scores in all age groups. In the OAB group, three mean SF‐36 scales (physical function [PF], VT, and MH) significantly improved after treatment. Conclusion: Treatment of OAB with solifenacin is associated with significant improvement in generic HRQoL and disease‐specific symptoms at 8 weeks after drug administration. Particularly for generic HRQoL as measured by the SF‐36, solifenacin treatment effectively improves three SF‐36 scores: PF, VT, and MH.     

Who Would Benefit from Solifenacin Add‐On Therapy to Tamsulosin for Overactive Bladder Symptoms Associated with Benign Prostatic Hyperplasia?

Objectives: We evaluated the types of patient factors that influence the efficacy and safety of solifenacin add‐on therapy to tamsulosin in men with overactive bladder (OAB) associated with benign prostatic hyperplasia (BPH). Methods: A total of 130 BPH patients with persistent OAB symptoms despite undergoing alpha1‐adrenagic antagonist monotherapy were enrolled in this study. Their OAB symptoms persisted after monotherapy consisting of tamsulosin 0.2 mg once daily for more than 8 weeks, followed by subsequent solifenacin 5 mg once daily. The patient backgrounds were assessed, as were the changes in their International Prostate Symptom score (IPSS), Quality of Life (QOL) index, and Overactive Bladder Symptom Score (OABSS) before and 8 weeks after the administration of solifenacin. Results: Total IPSS, QOL index, and OABSS improved significantly following solifenacin administration. Multivariate analyses revealed prostate volume was the only predictor that contributed to the improvement of total IPSS. In patients with prostate volume <30 mL, the improvement in total IPSS (?3.5) was superior to that for prostate volume >30 mL (?0.5; P = 0.002). The data also demonstrated that diabetes mellitus was an independent factor preventing OABSS improvement. In patients with diabetes mellitus, OABSS was not sufficiently improved (?0.6) compared to patients without diabetes (?2.1; P < 0.001). Conclusion: Solifenacin add‐on therapy to tamsulosin showed efficacy and good tolerability in BPH patients with OAB symptoms. The findings also indicated that patients with a relatively small prostate and without diabetes mellitus would receive more benefit from this therapy.     

Comparison of Outcome Assessments in Patients with Overactive Bladder Receiving Anticholinergics

Objectives: Patient‐reported outcomes (PRO) reflect treatment benefits from the patient's perspective, and are a subjective method of evaluating the efficacy of overactive bladder (OAB) treatment. We examined the changes in voiding diaries and health‐related quality of life (HRQL) according to patient‐perceived treatment benefits in patients with OAB receiving propiverine. Methods: Thirty‐two patients (mean age ± S.D: 55.1 ± 14.1 years) with OAB were treated with 20 mg propiverine once daily for 12 weeks. The 3‐day voiding diary and the Korean version of the Overactive Bladder Questionnaire (OABq), which includes an eight‐item bothersome symptom scale, as well as 25 HRQL items, were assessed at baseline and at 12 weeks. Finally, patient perception of treatment benefit was evaluated as “no benefit,”“little benefit,” or “much benefit” after treatment. Results: According to patients' perceptions of treatment benefits, 16 (50%) patients perceived “much benefit” from their treatment (group A) and 16 (50%) patients perceived “little benefit” or “no benefit” from their treatment (group B). In both groups, there were significant improvements in the micturation parameters, OABq bothersome symptoms, and total HRQL score after 12 weeks of treatment (P < 0.05). Although there were no significant differences in the voiding diary parameters between the two groups, patients in group A showed significant improvement of the OABq bothersome symptom and total HRQL score compared to group B (P < 0.05). Conclusion: Anticholinergic treatment improves both OAB symptoms and HRQL, and patients' perceptions of treatment benefits correlate better with the OABq than with the voiding diary parameters.     

Clinical Efficacy of α1‐Adrenargic Receptor Antagonist Naftopidil 75 mg/day in Patients with Benign Prostatic Hyperplasia

Objectives: The clinical efficacy and safety of 75 mg/day of naftopidil, an α1‐adrenargic receptor antagonist, was assessed in patients with benign prostatic hyperplasia (BPH). Methods: A total of 28 patients (mean age, 71.1 years; range, 46–86 years) with BPH were studied. Inclusion criteria were: (i) International Prostate Symptom Score (IPSS) ≥8; and (ii) quality of life (QOL) index ≥3. IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), and bladder diary (urinary frequency in daytime and nighttime, frequency of urinary incontinence and urgency) were evaluated before and 4 weeks after treatment with naftopidil at 75 mg/day. Results: Total IPSS and QOL index were significantly decreased after treatment. Total OABSS tended to decrease after treatment, with significant improvements in the “urgency” parameter. From the bladder diary, urinary frequency in daytime and nighttime and frequency of urgency were significantly decreased after treatment. Total IPSS and QOL index in patients with previous treatment were significantly improved after treatment, with significant improvements in the “incomplete emptying,”“poor flow” and “nocturia” parameters of IPSS. One case with a mild adverse effect of dizziness was encountered. Conclusion: These results suggest that administration of naftopidil at 75 mg/day was safe and effective for patients with BPH, regardless of the presence of previous treatment. This study indicates the feasibility of naftopidil at 75 mg/day as a first‐line treatment for men with BPH, or a second‐line treatment in cases with symptoms of incomplete emptying, poor flow and nocturia.     

Efficacy of Propiverine in Improving Symptoms and Quality of Life in Female Patients with Wet Overactive Bladder

Objectives: The present prospective study was conducted to assess the effects of propiverine hydrochloride in improving symptoms and quality of life (QoL) in female patients with wet OAB. Methods: Propiverine was administered orally for 8 weeks to 58 female patients who had urgency incontinence. Prior to administration, and at 4 and 8 weeks after administration, symptoms and QoL of the patients were assessed using a micturition diary, the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), and the King's Health Questionnaire (KHQ). In addition, the relationships between changes in frequency of urinary incontinence or amount of urine leakage following treatment and changes in each domain of the KHQ were investigated by multiple regression analysis. Results: After administration of propiverine, the mean numbers of daily micturitions, incontinence episodes, and urgency episodes assessed on the basis of the micturition diary significantly improved in comparison to the baseline: from 11.7 to 9.6 for daily micturitions, from 2.8 to 1.1 for incontinence episodes, and from 5.9 to 2.3 for urgency episodes in 8 weeks. The mean of the ICIQ‐SF total scores significantly decreased, from 8.4 to 4.6 points at 4 weeks and to 3.6 points at 8 weeks. The mean scores for three individual items in the ICIQ‐SF, namely, frequency of incontinence episodes, amount of leakage, and impact on everyday life also significantly improved. The KHQ scores significantly improved at both 4 and 8 weeks post‐administration in all domains except personal relationships. In the multiple regression analysis, improvement in frequency of incontinence was significantly related to the domain of severity measure of the KHQ, while improvement in amount of leakage was significantly related to the domains of general health perception and social limitations. Conclusion: Propiverine hydrochloride contributed to improvements not only in symptoms but also in QoL in female patients with wet OAB.     

Efficacy,Safety and Tolerability of Fesoterodine in Asian Patients with Overactive Bladder

Objectives: To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg once daily (QD) compared with placebo in Asian subjects with overactive bladder (OAB) after 12 weeks of treatment. Methods: This phase II, dose‐finding study consisted of a 2‐week placebo run‐in period followed by a 12‐week, randomized, double‐blind, placebo‐controlled, treatment period. Eligible subjects were aged ≥20 years with ≥8 micturitions per 24 h and ≥1 urgency urinary incontinence (UUI) episodes per 24 h reported in a 3‐day diary. The subjects were randomized to receive placebo, fesoterodine 4 mg, or fesoterodine 8 mg QD for 12 weeks. Results: Of 1232 subjects who entered the placebo run‐in period, 951 received double‐blind treatment. The mean number of UUI episodes per 24 h at baseline was 2.2 among the three treatment groups. The two fesoterodine groups showed statistically significant decreases from baseline in the mean number of UUI episodes per 24 h at week 12 (primary endpoint) compared with placebo. Most all‐causality adverse events (e.g. dry mouth and constipation) were mild or moderate. The percentage of subjects with severe adverse events was low and similar among the treatment groups (placebo, 1.3%; fesoterodine 4 mg, 1.9%; fesoterodine 8 mg, 1.0%). Conclusion: Fesoterodine 4 and 8 mg QD were significantly better than placebo in improving OAB symptoms. Overall, the two fesoterodine dosing regimens were well tolerated. These results suggest that fesoterodine 4 and 8 mg QD are effective and well‐tolerated treatments for OAB in Asian subjects.     

Pharmacologic management of overactive bladder

Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.     

Randomized Controlled Trial to Treat Benign Prostatic Hyperplasia with Overactive Bladder Using an Alpha‐blocker Combined with Anticholinergics

Objectives: TAABO was a randomized, controlled trial to evaluate the efficacy and safety of combination therapy of tamsulosin (TAM) with propiverine (PROP) in men with both benign prostatic hyperplasia and overactive bladder. Methods: It enrolled men 50 years or older who had an international prostate symptom score (IPSS) of 8 or higher, an urgency item score of 1 or higher, and a quality of life (QOL) score of 2 or higher. After 8 weeks of TAM 0.2 mg/day, patients who met the inclusion criteria (8 micturitions per 24 h and 1 urgency per 24 h, evaluated by bladder diary) and were eligible for 12‐weeks of continued Treatment II. Five hundred and fifteen patients were enrolled. Thereafter, 214 patients were assigned randomly to receive either TAM alone (n = 67), TAM plus PROP 10 mg (n = 72), or TAM plus PROP 20 mg (n = 75) in Treatment II. The primary efficacy end point was a change in micturitions per 24 h documented in the bladder diary. The change from baseline in urgency episodes per 24 h, IPSS, IPSS/QOL subscore, urinary flow rate and postvoid residual volume were assessed as secondary efficacy measures. Results: A total of 141 men (47 TAM, 49 TAM plus PROP 10 mg, and 45 TAM plus PROP 20 mg patients) were assessed by week 12. Compared with the TAM, TAM plus PROP 10 mg patients experienced significantly fewer micturitions (P = 0.0261), urgencies (P = 0.0093) per 24 h, lower IPSS storage (P = 0.0465), and IPSS urgency (P = 0.0252) subscores. Conclusions: These results suggest that combining TAM and 10 mg of PROP for 12 weeks provides added benefit for men with both benign prostatic hyperplasia and overactive bladder.     

Prevalence of xerostomia with or without overactive bladder symptoms

Overactive bladder (OAB) occurs idiopathic or secondary to a neurological cause. In addition, OAB may also occur due to xerostomia, because it causes excessive drinking of water. If xerostomia is one of the causes of OAB, treating xerostomia may be effective. This study aimed to investigate the prevalence of xerostomia with or without overactive bladder symptoms. A web-based questionnaire was administered to investigate the prevalence of xerostomia with or without overactive bladder symptoms. The survey included questions concerning age, gender, medical history, medications, OAB symptoms by the Overactive Bladder Symptom Score (OABSS), and xerostomia by the Dry Mouth Scale (DMS). From the analysis, a total of 21 (13.0%) participants were identified as having OAB. The prevalence of xerostomia was six (28.6%) in the OAB group and 14 (10.0%) in the non-OAB group. OABSS and DMS were significantly higher in the OAB group than in the non-OAB group. Urgency score and urgency incontinence score of OABSS were substantially higher in xerostomia participants than non-xerostomia participants. The adjusted odds ratio of OAB showed DMS total score, xerostomia symptoms, accompanying symptoms, and other symptoms that were all significantly associated with OAB. These results suggested that OAB subjects, even untreated subjects, had xerostomia. It may be beneficial for clinicians to perform dry mouth management in parallel with careful choice pharmacotherapy for the wellness of OAB patients.     

Defining Causes for Overactive Bladder Symptoms in Women

Objectives: The aim of the present study was to determine the causes for overactive bladder (OAB) symptoms in women visiting a urological clinic. Methods: We prospectively recruited female patients with OAB symptoms between December 2008 and February 2010. All patients were interviewed for their detailed personal and medical history. All patients completed a 3‐day frequency‐volume chart. Symptom severity was evaluated using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) questionnaires. All patients underwent either conventional pressure‐flow urodynamic studies or video‐urodynamic studies. On the basis of these evaluations, patients were assigned to one of the following categories: idiopathic OAB, stress urinary incontinence (SUI)‐associated, neurogenic bladder, or bladder outlet obstruction (BOO). Results: A total of 108 female patients were recruited into the study. The mean age of the patients was 63.75 ± 14.02 years (range: 23–89). Detrusor overactivity was demonstrated in 55 patients (51%). The differential diagnosis was idiopathic OAB in 51 women (47.2%), SUI‐associated in 46 (42.6%), neurogenic bladder in 13 (12.0%) and BOO in 7 (6.5%). Conclusion: Our study suggests that the causes for OAB symptoms could be defined in half of the women visiting a urological clinic. Among them, SUI was the most common. Moreover, OAB symptoms in women might relate to BOO. Detailed history taking and sophisticated urodynamic studies are required for a substantial group of female patients with OAB symptoms to make the correct diagnosis and provide optimal therapy.     

Potential Primary Endpoint for Exploratory Clinical Trial in Patients with Overactive Bladder: A Systematic Literature Review

Objectives

To identify a potential primary endpoint in an early‐phase exploratory trial among key overactive bladder (OAB) symptoms.

Methods

Placebo‐controlled double‐blinding trials in patients with OAB were extracted for systematic literature review. The correlation between key OAB symptoms recorded in bladder diaries and coefficient of variation (CV) in each study were assessed.

Results

Forty‐one controlled trials were extracted for the present review. Mean number of urgency episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h, mean volume voided per micturition, and mean number of micturitions in 24 h (Spearman's r = 0.725, ?0.661, and 0.657, respectively). Mean number of micturitions in 24 h was also substantially associated with mean volume voided per micturition (Spearman's r = ?0.674). Mean number of incontinence episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h and mean volume voided per micturition (Spearman's r = 0.840 and ?0.628, respectively). The median CV of mean volume voided per micturition in each trial was the smallest among all endpoints.

Conclusions

Our findings suggest that volume voided per micturition is a useful symptom for evaluating OAB candidate compounds in a small sample size and represents an effective primary endpoint, especially in exploratory clinical trials.     

Modulation of Bladder Afferent Activity by Propiverine and its Active Metabolites (M‐1 and M‐2) in Rats

Objectives: To evaluate the effects of propiverine and its active metabolites (M‐1 and M‐2) on bladder function through modulation of afferent activity in rats. Methods: Cystometry was performed in urethane anesthetized female rats. We examined the effects of intravesical administration of propiverine, M‐1 and M‐2 on bladder overactivity induced by oxotremorine‐M (Oxo‐M; non‐selective mAChR agonist). Results: Intravesical administration of Oxo‐M (200 µM) elicited bladder overactivity as evidenced by decreased intercontraction interval (ICI) and pressure threshold (PT) without changing maximum voiding pressure or baseline pressure. These effects were blocked by intravesical administration of propiverine (30 µM) or M‐2 (300 µM). Intravesical administration of M‐1 (30 µM) alone increased ICI and PT, but did not prevent Oxo‐M‐induced decreases in ICI and PT. Conclusion: These results suggest that propiverine and M‐2 have anticholinergic effects on bladder afferent activity and that M‐1 has an inhibitory effect through the mechanism other than muscarinic receptor modulation. Thus, clinical benefits of propiverine in patients with overactive bladder could be mediated by multiple actions of propiverine and its active metabolites.     

琥珀酸索利那新治疗良性前列腺增生术后膀胱过度活动症的临床疗效观察

目的 探讨琥珀酸索利那新治疗良性前列腺增生(BPH)术后并发膀胱过度活动症(OAB)的临床疗效和安全性.方法 115例接受BPH手术的患者中,治疗组(n=58)术后第4d睡前口服索利那新治疗20 d,对照组(n=57)术后服用莨菪碱片,观察患者在拔出导尿管前后排尿情况,并以尿动力学检查、国际前列腺症状评分(IPSS)和膀胱过度活动症评分(OABSS)评价患者排尿情况.结果 治疗组IPSS评分由28.3分下降到11.3分,OABSS评分由(14.2±1.2)分下降到(2.9±0.7)分(P＜0.01).对照组IPSS评分由27.3分下降到11.8分(P＜0.01),OABSS评分由(14.2±1.6)分下降到(11.3±1.1)分,治疗前后差异无统计学意义(P＞0.05).结论 BPH术后正确地使用索利那新,能缓解膀胱过度活动给患者带来的痛苦症状,有利于患者的术后康复.     

Mirabegron versus vibegron in previously untreated female patients with overactive bladder: A randomized,single-clinic,open-label trial

Objectives

This study aimed to assess the efficacy and safety of mirabegron compared with vibegron (both 50 mg once daily) in Japanese female patients with symptoms of overactive bladder (OAB).

Methods

This prospective, 12-week, two-arm, parallel-group, open-label randomized trial (UMIN000038288) was conducted at a single clinic from December 2019 to September 2022. The primary efficacy outcome measure was the change in mean total overactive bladder symptom scores (OABSSs) from baseline to end of treatment (EOT) (Week 12). The secondary efficacy outcome measures were changes in mean International Prostate Symptom Score from baseline to EOT, the ratio of patients who achieved a minimal clinically important change (MCIC) of total OABSS, and individual domains of the King's Health Questionnaire. Safety assessments, such as adverse events (AEs), postvoid residual volume, and patient-reported incidences, were recorded at every visit.

Results

There was no statistically significant adjusted mean difference between mirabegron and vibegron in terms of the primary outcome of the mean change from baseline to EOT in the total OABSS. The difference in the percentage of patients in the mirabegron and vibegron groups achieving an MCIC on the total OABSS was not statistically significant but appeared to be clinically important. The incidence of treatment-related AEs was significantly higher for the vibegron group (38.5%) than the mirabegron group (19.1%) (p = .047).

Conclusions

These results showed that both drugs were effective in female OAB patients, with no significant differences in terms of efficacy. However, the safety of vibegron requires further investigation.     

Lower urinary tract symptoms are elevated with depression in Japanese women

Objectives

Depression might worsen lower urinary tract symptoms (LUTS), but the correlation is still disputed. This study examined the influence of depression on LUTS in Japanese women.

Methods

This study used a web-based questionnaire to evaluate the mental status of depression and LUTS. The mental status of depression was evaluated using the Quick Inventory of Depressive Symptomatology-Japanese version (QIDS-J), and LUTS was assessed based on the Overactive Bladder Symptom Score (OABSS) and responses to the International Consultation on Incontinence Questionnaire-Short Form.

Results

A total of 4151 of 5400 (76.9%) women responded to the questionnaire. The mean age was 48.3 ± 13.8 years. The OABSS gradually increased with the QIDS-J score. The incidence of overactive bladder (OAB) and urgency urinary incontinence (UUI) also increased along with the QIDS-J score. In the younger age group (20–39 years old), the risks of OAB and UUI were higher than in the elderly group (7.42 for OAB and 7.44 for UUI).

Conclusions

This study revealed that worsening of LUTS was correlated with depression.     

Does the Number of Previous Vaginal Deliveries Affect Overactive Bladder Symptoms and their Response to Treatment?

Objectives: To explore associations between the number of vaginal deliveries (primary aim) or gender (secon‐ dary aim) and overactive bladder (OAB) symptoms as well as their response to treatment with a muscarinic antagonist. Methods: Preplanned secondary analysis of an observational study of solifenacin in OAB patients. Episode frequencies of OAB symptoms, pad use and scores on OAB rating scales were documented in 4450 patients before and after a 12–14 week treatment period with solifenacin 5 or 10 mg. Results: Women without, and with one, two or more than two vaginal deliveries and men were similar in their baseline characteristics. All groups also exhibited rather similar reductions in symptoms and improvements in rating scales upon treatment. Conclusion: These data indicate that solifenacin, and perhaps other muscarinic receptor antagonists, are similarly suitable for the treatment of OAB symptoms in both genders, irrespective of previous vaginal deliveries.     

Synergistic Effect by Co‐Administration of Tamsulosin and Solifenacin on Bladder Activity in Rats

Objectives: We examined the effects of alpha1‐adrenoceptor antagonist (tamsulosin hydrochloride) and antimuscarinic agent (solifenacin succinate) alone or in combination on the urinary adenosine triphosphate (ATP) level and cystometric parameters before and after bladder stimulation. Methods: Female rats were administered tamsulosin hydrochloride (0.5 or 3 µg/kg/h) and/or solifenacin succinate (20 or 100 µg/kg/h) via a subcutaneously implanted osmotic minipump. Rats receiving distilled water were used as control. After 2 weeks, continuous cystometry with physiological saline or 0.1% acetic acid solution was performed. Urinary ATP level was also measured before and after stimulation by 0.1% acetic acid solution. Results: During cystometry with bladder stimulation, the interval between voiding became shorter and the maximum voiding pressure (MVP) became higher in the control group. In the high‐dose tamsulosin and solifenacin groups, the inhibition of urinary frequency was observed. The MVP also became higher in the high‐dose tamsulosin group, but such a change was not seen in the high‐dose solifenacin group. In case of low‐dose administration, either agent alone did not inhibit the increase of urinary frequency and MVP due to bladder stimulation. However, co‐administration of these ineffective low doses of tamsulosin and solifenacin resulted in the inhibition of urinary frequency. The high‐dose or low‐dose solifenacin group and the co‐administration group showed similar inhibition of the increase of urinary ATP after bladder stimulation. Conclusion: Tamsulosin may have a different effect on the bladder and/or the neuronal pathways that is unrelated to ATP, so the combination of tamsulosin and solifenacin may synergistically inhibit urinary frequency after bladder stimulation.     

Summary of Anticholinergic Pharmacotherapy Available for Overactive Bladder

The International Continence Society definition of overactive bladder syndrome (OAB) is “urgency, with or without urge incontinence, usually with frequency and nocturia.” OAB syndrome is a very common condition, estimated to affect 12% to 22% of women and men in Europe and 16% to 17% in the United States. The muscarinic receptor antagonists are first-line pharmacotherapy in treatment of OAB. In North America, six antimuscarinic drugs are marketed for treating OAB: oxybutynin, tolterodine, fesoterodine, trospium, darifenacin, and solifenacin. In our review, we summarize the pharmacology, efficacy, and adverse events of commonly used anticholinergic agents.     

Mirabegron causes vesical and urethral relaxation in rats with spinal cord injury

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03–3 mg/kg) or mirabegron (0.03–3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non‐voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.