Propiverine Group Research Articles

Safety and Efficacy of Intermittent versus Continuous Anticholinergic Medication in Management of Overactive Bladder in Adult

Background: overactive bladder (OAB) also referred to as the urgency-frequency syndrome, with or without urge urinary incontinence can considerably impair the patient's quality of life. It is widely accepted that diet and life style modifications, behavioral therapy and medication belong to the standard conservative therapeutic options and considered as the first-line measures. The International Consultation on Incontinence (ICI) guidelines reported that when the first line approach is not fully satisfactory or fails after 8-12 weeks, alternative therapies should be sought out. It is worthwhile and justified to proceed to second-line therapy if patients are refractory to antimuscarinic therapy or if the treatment is contraindicated. Second-line of therapies include less-invasive measures such as percutaneous posterior tibial neve stimulation, sacral neuromodulation, detrusor injections with botulinum toxin (BTX) and whereas more-invasive measures constitute surgical techniques e.g. bladder augmentation or substitution. Pelvic neuromodulation has been proven effective and is today an established treatment option for patients refractory to or intolerant of conservative treatments. Objective: this study aimed to compare between the efficacy of continuous anticholinergic therapy and intermitted anticholinergic therapy for treatment of the overactive bladder. Patients and Methods: our study included 60 patients categorized into two groups: continuous anticholinergic therapy group and intermitted anticholinergic therapy. By using 12 weekly intermitted anticholinergic therapies, remarkable clinical results were obtained. Percent of the patients who complained OAB in the intermitted anticholinergic group reported a statistically significant subjective success. These patients chose to continue treatment to maintain the response. Results: patients in the intermitted anticholinergic therapy group showed significant improvement of frequency (31%) urgency (50%) urge incontinence (50%) and nocturia (53%) compared to propiverine group frequency (50%) urgency (60%) urge incontinence (67%) and nocturia (67%). No serious side effects were reported, in group A 8 patients had horm of dry mouth in 5 cases (16.7%), constipation in 2 cases (67%) 8 blurred vision in one case (33%). In group B, there were 5 patients (16.7%) in the horm of dry mouth in 3 cases (10% constipation in one case (3.3) and blurred vision in one case (3.3%). Conclusion: our study concluded that intermittent anticholinergic therapy induced improvement of bladder over activity symptoms and less side effects than continuous anticholinergic group.

Efficacy and safety of once‐daily oxybutynin patch versus placebo and propiverine in Japanese patients with overactive bladder: A randomized double‐blind trial

To evaluate the efficacy and safety of once-daily oxybutynin patch therapy for overactive bladder. A randomized double-blind trial was carried out in patients with overactive bladder syndrome, who received an oxybutynin patch, propiverine (20 mg) or placebo once daily for 12 weeks. The primary efficacy end-point was the change of the mean daily number of micturitions in week 12. A total of 1530 patients were randomized to receive the oxybutynin patch (573), propiverine (576) or placebo (381). The change of the mean daily frequency of micturition from baseline in the full analysis set was -1.89 ± 2.04 with the oxybutynin patch, which was significantly higher than with placebo (-1.44 ± 2.23) (P = 0.0015). The difference of the mean change in the mean daily number of micturitions between the oxybutynin patch and propiverine groups showed a 95% confidence interval of -0.28 to 0.21, and the upper limit of this interval was below the predefined non-inferiority margin of 0.37, showing non-inferiority of the oxybutynin patch to propiverine. The incidence of dry mouth and constipation was higher with propiverine than with the oxybutynin patch or placebo. Application site dermatitis was more frequent with the oxybutynin patch (31.8%) than with propiverine (5.9%) or placebo (5.2%), but the dermatitis was generally mild. This trial shows the efficacy of the new once-daily oxybutynin patch for overactive bladder. Despite a higher rate of dermatitis with the oxybutynin patch, dry mouth and constipation occurs less often than during treatment with propiverine.

Effects of propiverine hydrochloride, an anticholinergic agent, on urethral continence mechanisms and plasma catecholamine concentration in rats

Anticholinergics are used to treat overactive bladder. Anticholinergic agents such as propiverine hydrochloride reportedly increase plasma catecholamine levels in rats. It is also known that active urethral closure mechanisms prevents stress urinary incontinence (SUI), which is enhanced by central and peripheral noradrenergic system activation. Therefore, we examined the influence of propiverine hydrochloride on urethral anti-incontinence function in rats. Adult female rats were divided into propiverine and vehicle-treated groups. The propiverine group was given propiverine orally once a day for 2 weeks, after which urethral function and plasma concentrations of catecholamine (dopamine, norepinephrine, epinephrine) were tested. Urethral baseline pressure measured by a microtransducer-tipped urethral catheter and leak-point pressure during passive intravesical pressure elevation were significantly increased in the propiverine group compared with the vehicle group. Plasma norepinephrine and epinephrine levels in the propiverine group were also significantly increased. Propiverine treatment that increases plasma catecholamine levels could contribute to improvement of SUI conditions by increasing urethral resistance.

Randomized, Single-Blind, Parallel Study of the Effectiveness and Safety of Solifenacin versus Propiverine in the Treatment of Overactive Bladder.

To compare the effectiveness and safety of solifenacin versus propiverine in the treatment of overactive bladder (OAB), in a single-blind, randomized parallel study. Sixty-six patients with OAB (14 men and 52 women) were randomly assigned to groups: solifenacin (5 mg/day) or propiverine (20 mg/day) and treated for 8 weeks. The primary outcome variable was mean change from baseline to end of treatment in urgency of the OAB symptom score (OABSS). Secondary outcomes were bladder diary variables: change over 24 h in the mean number of voids (daytime and nighttime), episodes of micturition urgency and incontinence, and mean volume voided. Patients also completed total OABSS and the King's Health questionnaires. Group backgrounds were comparable except for the male to female proportion; 11:22 for solifenacin (n = 33) versus 3:30 for propiverine (n = 33). Adverse events were 6 of 29 (21%) for solifenacin versus 14 of 26 (54%) for propiverine (P = 0.017). Three patients were withdrawn for voiding difficulty (one in solifenacin and two in propiverine) and one patient for dry mouth (propiverine group). Change in OABSS urgency score was -2.3 ± 1.4 for solifenacin (n = 28) versus -1.3 ± 1.7 for propiverine (n = 23), (P = 0.0169). Total OABSS and other individual scores, and voiding diary parameters for both drugs showed improvements; however, between-group difference was not established. Although both solifenacin 5 mg and propiverine 20 mg were effective in the treatment of OAB, solifenacin appeared to be more effective and tolerable.

Excitatory effect of propiverine hydrochloride on urethral activity in rats

To investigate the effects of the antimuscarinic agent, propiverine, on the bladder and urethra in rats. A total of 54 female rats were given propiverine, imidafenacin (an antimuscarinic agent), or distilled water by gavage once or twice daily. After 2 weeks, bladder and urethral activity were recorded under urethane anesthesia. In the propiverine group, the changes of bladder and urethral activity before and after intravenous injection of α(1) -adrenergic antagonists (prazosin, silodosin and naftopidil) were also recorded. Furthermore, the leak point pressure after electrical stimulation of abdominal wall muscles was measured in rats with vaginal distension from the control and propiverine groups. Intravesical baseline pressure was significantly lower in the propiverine and imidafenacin groups compared with the control group, whereas the urethral baseline pressure was significantly higher in the propiverine group compared with the control or imidafenacin groups. Intravenous injection of prazosin (an α(1) -receptor antagonist) significantly decreased the urethral baseline pressure in both of the propiverine and control groups. Intravenous injection of silodosin and naftopidil (α(1A) - and α(1D) -receptor antagonists, respectively) significantly decreased the maximum contraction pressure and the urethral baseline pressure in the propiverine group. The leak point pressure of the propiverine group was significantly higher than that of the control group. An increase of catecholamines after propiverine administration might activate smooth muscle of the proximal urethra via α(1A) - and α(1D) -adrenergic receptors, as well as activating urethral and pelvic floor striated muscle via the spinal motoneurons.

Efficacy of propiverine, an anticholinergic agent, in young and old rats

Aims We examined the influence of propiverine hydrochloride, an anticholinergic agent, on the micturition reflex, blood pressure, and plasma catecholamine levels in young rats and old rats. Main method Male F344/DuCrlCrlj Fischer rats (young rats aged 2 months and old rats aged 26 months) were divided into the following 4 groups: a young sham group, an old sham group, a young propiverine group, and an old propiverine group. Rats from the young (body weight: 215 ± 7 g) or old propiverine groups (body weight: 414 ± 22 g) were administered propiverine hydrochloride (5 or 10 mg, respectively) dissolved in distilled water (0.5 mL) into the stomach through a fine catheter once daily. Rats from the young and old sham groups were administered the same volume of distilled water. After 2 weeks of treatment, continuous cystometry was done with physiological saline and 0.1% acetic acid, and measurement of plasma catecholamines, blood pressure, and heart rate was performed. Key findings The old rats had a longer interval between bladder contractions and higher plasma catecholamine levels than the young rats. Bladder stimulation by 0.1% acetic acid induced frequency in both young and old rats. Administration of propiverine inhibited the induction of frequency in the old rats, but not in the young rats. Propiverine increased plasma catecholamine levels in the young rats, but not in the old rats. Significance These findings show that bladder activity varies with aging, and the response to propiverine also changes in an age-related manner.

Propiverine hydrochloride in Japanese patients with overactive bladder: A randomized, double‐blind, placebo‐controlled trial

The aim of this study was to investigate the efficacy and safety of propiverine for overactive bladder (OAB) in Japanese patients. In this multicentre, randomized, double-blind study, patients ≥ 20 years old with symptoms of OAB for ≥ 12 weeks were allocated to either propiverine (20 mg once daily) or placebo for 12 weeks. Efficacy and quality of life were assessed using a 7-day bladder diary, the OAB symptom score, and King's Health Questionnaire. Safety was mainly assessed by adverse events and the QTc interval. A total of 567 patients were allocated. Change in number of micturitions/24 h was significantly greater in the propiverine group than in the placebo group (-1.86 vs-1.36, P = 0.001). Compared to placebo, propiverine produced significant improvements in urgency, urgency incontinence, urine volume/micturition, and the OAB symptom score. Significant improvements in urgency, urgency incontinence, and micturition frequency were observed at the first 4 weeks of treatment. All nine domains of King's Health Questionnaire were improved more with propiverine than with placebo. Adverse effects with propiverine were mostly mild, and no patient developed QTc interval prolongation exceeding 500 ms. Propiverine is effective for Japanese OAB patients by improving their symptoms and quality of life with a predictable side-effect profile.

Urinary urgency outcomes after propiverine treatment for an overactive bladder: the ‘Propiverine study on overactive bladder including urgency data’

To investigate the effects of a daily regimen of propiverine 20 mg in patients with an overactive bladder (OAB), focused on improving urgency, as the clinical efficacy of treatment for OAB should be measured in terms of urgency, the cornerstone symptom of OAB. Eligible patients aged > or = 18 years with symptoms of OAB were enrolled in this multicentre, prospective, parallel, double-blind, placebo-controlled trial. Of 264 patients (mean age 52.2 years), 221 who had efficacy data available from baseline and at least one on-treatment visit with >75% compliance with medication were analysed (142 in the propiverine group and 79 in the placebo group). All patients were randomized to receive a placebo or 20 mg propiverine once daily in a 12-week study. They completed a 3-day voiding diary before visits during the study period, including the severity of urgency associated with every voiding, using the Indevus Urgency Severity Scale and the Urgency Perception Score. The patients' overall self-evaluation of treatment benefits at the end of the study, and safety data, were also collected. The daily urgency episodes reduced significantly from baseline to 12 weeks on propiverine treatment, compared with placebo (-46.0% vs -31.3%, P = 0.005). Secondary endpoints, including sum of urgency severity per 24 h, urgency severity per void, and daytime voiding frequency, were also improved significantly in the propiverine group. Overall, of those patients treated with propiverine, 38.7% rated their treatment as providing 'much benefit', compared with 15.2% of the placebo group (P = 0.025). Adverse events reported by 32 (22.5%) and 10 (12.7%) patients in the propiverine and placebo group were all tolerable. However, this is a short-term study using only one fixed regimen. Propiverine 20 mg once-daily could be an effective treatment for patients with OAB, by improving urgency.

A randomized, double‐blind, placebo‐ and propiverine‐controlled trial of the novel antimuscarinic agent imidafenacin in Japanese patients with overactive bladder

To compare the efficacy and tolerability of imidafenacin, a novel antimuscarinic agent, with propiverine and a placebo in Japanese patients with overactive bladder (OAB). Men and women having OAB symptoms were randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20 mg of propiverine once daily, or a placebo for 12 weeks, and assessed for efficacy and safety. Overall, 781 patients were randomized to imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of treatment, a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group (P < 0.0001). The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes (P = 0.0014, non-inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of adverse events with imidafenacin was significantly lower than with propiverine (P = 0.0101). Dry mouth, the most common adverse event, was significantly more common in the propiverine group than in the imidafenacin group (P = 0.0302). There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval, whereas there was a significant increase in the mean QTc interval in the propiverine group (P < 0.0001), but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups. The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes, and well tolerated for the treatment of OAB symptoms.

Comparison of the effect of anti-muscarinic agents on bladder activity, urinary ATP level, and autonomic nervous system in rats

We compared the effect of 4 anti-muscarinic agents on bladder activity, urinary ATP levels, and autonomic nervous system in rats. Rats were divided into the following 5 groups (control group, oxybutynin group, propiverine group, tolterodine group, imidafenacin group), and were administered daily the designated anti-muscarinic agent or distilled water into the stomach. After 2 weeks, we performed 1) continuous cystometry with physiological saline and 0.1% acetic acid solution, 2) measurement of urinary ATP level before and after bladder stimulation, and 3) measurement of the heart rate, blood pressure and plasma catecholamines. The maximum bladder contraction pressure increased and the interval between contractions became shorter during cystometry with acetic acid solution in the control group, but not in the 4 anti-muscarinic agent groups. The urinary ATP level increased after bladder stimulation in all groups, but the increase was smaller in the propiverine and imidafenacin groups. The plasma noradrenaline and dopamine levels of the propiverine group were higher. Taken together, all anti-muscarinic agents inhibited the bladder activity without changing the heart rate and blood pressure. Especially, the inhibitory effect of propiverine and imidafenacin on bladder activity may be partly due to blocking an increase of ATP release from the bladder urothelium.

Effects of propiverine and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats

We examined the effects of propiverine hydrochloride and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats. Thirty-nine female rats were divided into a control group, a propiverine group, and a naftopidil group. Rats in the propiverine and naftopidil groups were administered 1 ml/day of propiverine or naftopidil dissolved in water at 5mg/ml, while animals in the control group were administered 1 ml of water only. After 2 weeks, 18 rats (6 per group) underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and their bladder activity was recorded. In the remaining 21 rats (7 per group), 0.1% acetic acid solution was infused into the bladder and the urinary ATP level was measured before and after stimulation (days 0-7). During cystometry with acetic acid in the control group, the interval between bladder contractions was shorter and the maximum bladder contraction pressure was higher than the results for cystometry with physiological saline. The maximum bladder contraction pressure was also increased in the naftopidil group, but such a change was not seen in the propiverine group. The urinary ATP level increased significantly in all three groups after the infusion of acetic acid, but the increase of ATP was smaller in the propiverine group (45% of control) and the naftopidil group (62% of control) than in the control group on day 0. Therefore, the inhibitory effect of propiverine and naftopidil on bladder activity may be partly due to blocking ATP release from the bladder epithelium.

Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome

Aim: To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder. Methods: This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed. Results: A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg ≤ propiverine 45 mg ≤ propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate. Conclusions: Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.

Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome

To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder. This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed. A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg </= propiverine 45 mg </= propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate. Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.

Propiverine Compared to Oxybutynin in Neurogenic Detrusor Overactivity – Results of a Randomized, Double-blind, Multicenter Clinical Study

ObjectivesTo compare the efficacy and tolerability of propiverine and oxybutynin in patients with neurogenic detrusor overactivity. MethodsPatients were eligible, if at least 18 years of age and suffering from neurogenic detrusor overactivity. Eligibility also required a maximum cystometric capacity less than 300ml. After a one-week run-in period, propiverine 15mg t.i.d. or oxybutynin 5mg t.i.d. were administered for 21 days. As primary efficacy outcomes urodynamic parameters were assessed. As tolerability outcome the percentage of patients with newly manifesting anticholinergic adverse events was taken. Results131 patients were recruited at 20 study centers. The maximum cystometric capacity (ml) was increased significantly in the propiverine group from 198 (±110) to 309 (±166), and in the oxybutynin group from 164 (±64) to 298 (±125). Similarly, maximum detrusor pressure during the filling phase (cm H2O) was lowered significantly in the propiverine group from 56.8 (±36.2) to 37.8 (±31.6), and in the oxybutynin group from 68.6 (±34.5) to 43.1 (±29.2). No significant differences resulted between treatment groups.Anticholinergic adverse events were reported less frequently in the propiverine compared to the oxybutynin group (63.0% versus 77.8%). Dryness of the mouth, the most frequent adverse event, was reported significantly less (47.1% versus 67.2%; p=0.02) in the propiverine compared to the oxybutynin group. ConclusionPropiverine and oxybutynin are equally effective in increasing bladder capacity and lowering bladder pressure in patients with neurogenic detrusor overactivity. The trend for better tolerability of propiverine compared to oxybutynin achieved significance for dryness of the mouth.

Propiverine versus Tolterodine: Efficacy and Tolerability in Patients with Overactive Bladder

Objectives: Propiverine and tolterodine were compared with respect to efficacy, tolerability and impact on the quality of life in the treatment of patients with idiopathic detrusor overactivity. Methods: In a randomised, double-blind, multicentre clinical trial, patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2 mg tolterodine twice daily over a period of 28 days. The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy. The difference of both values was used as the primary endpoint. Secondary endpoints were voided volume per micturition, evaluation of efficacy (by the investigator), tolerability, post void residual urine, and quality of life. Results: The mean maximum cystometric capacity increased significantly ( p < 0.01) in both groups. The volume at first urge and the frequency/volume chart parameters also showed relevant improvements during treatment. 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events. The most common adverse event, dry mouth, occurred in 20 patients in the propiverine group and in 19 patients in the tolterodine group. The scores for the quality of life improved comparably in both groups. Conclusion: The study demonstrates comparable efficacy, tolerability, and improvement in the quality of life of 15 mg propiverine twice-daily and 2 mg tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor overactivity.