Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity

Purpose To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study. Materials and Methods One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison. Results IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1. Conclusion This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS. In patients with OAB or DO, long term anticholinergic treatment may be regarded as a treatment option. .

Efficacy and Safety of Propiverine in Children with Overactive Bladder

PURPOSE: Antimuscarinic therapy remains one of the most common forms of therapy for overactive bladder (OAB) in children. However, few clinical studies on the outcomes of antimuscarinics in children with OAB have been published. Therefore, we evaluated the efficacy and safety of propiverine, which is frequently prescribed for the treatment of pediatric OAB. MATERIALS AND METHODS: We retrospectively reviewed children with OAB treated with propiverine within the past 5 years. The response rates were compared between the non-urge incontinence (non-UI) and urge incontinence (UI groups). The cumulative response rate by treatment duration was also compared between the two groups. RESULTS: Among a total of 68 children, 50 children (73.5%) experienced UI. The overall response rate was 86.8%. Functional bladder capacity after treatment was 150 ml, which represented an increase compared with the value (140 ml) before treatment. The voiding frequency per day decreased from 14.0 to 8.5 times. The overall response rate (88.0%) in the non-UI group was not significantly different from that seen in the UI group (83.3%; p>0.05). In non-UI children, the cumulative response rates were 36.0%, 54.0%, 68.0%, 74.0%, 76.0%, and 78.0% at 4, 8, 12, 16, 20, and 24 weeks, respectively. The cumulative response rates in the UI children were 11.1%, 33.3%, 44.4%, 50.0%, 50.0%, and 55.6%, respectively during the same respective time periods. Adverse effects were identified in only two (2.9%) patients, and neither case was severe. CONCLUSIONS: Propiverine is effective and well tolerated as a treatment for children suffering from OAB with or without UI.

Efficacy and Safety of Low-Dose Propiverine in Patients with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia with Storage Symptoms: A Prospective, Randomized, Single-Blinded and Multicenter Clinical Trial

PURPOSE: The aim of this study was to evaluate whether low-dose anticholinergics combined with an alpha1-receptor antagonist would continue the effect of an alpha-blocker, decrease the side effects of anticholinergics, and improve the symptoms of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). MATERIALS AND METHODS: Two hundred nine men with LUTS/BPH with storage symptoms (International Prostate Symptom Score [IPSS] > or =12; storage symptoms > or =4) were randomly assigned in a prospective, multicentered, and single-blind fashion to either the control group (alfuzosin 10 mg, once daily) or the combined group (alfuzosin 10 mg, once daily, and propiverine 10 mg, once daily) for 2 months. IPSS, maximal urinary flow rate (Qmax), and postvoid residual volume (PVR) were used to grade symptoms, side effects, and the impact on quality of life (QoL) at the start of the study and after 1 and 2 months. RESULTS: There were no significant differences in patient background, including age, prostate size, Qmax, and PVR, between the control group and the combined group. In the combined group, the IPSS total score and the IPSS storage symptom score were significantly improved compared with the control group. The IPSS voiding symptom score, QoL, Qmax, and PVR did not differ significantly. There were no serious side effects in either group. CONCLUSIONS: Management with an alpha1-receptor antagonist combined with a low-dose anticholinergic improved the total score and storage symptom score of the IPSS compared with alpha1-receptor antagonist only group without causing serious side effects. This initial combination medication can be considered an effective and safe treatment modality for LUTS/BPH patients with storage symptoms.

Urodynamic Effects of Propiverine on Detrusor Overactivity and Abdominal Straining during Voiding in Awake Rats with Intravesical Prostaglandin E2 Instillation

PURPOSE: We investigated the effect of propiverine on cystometric parameters based on intraabdominal pressure (IAP) in awake rats in an overactive bladder (OAB) model induced by intravesical instillation of prostaglandin E2 (PGE2). MATERIALS AND METHODS: Twenty-two female Sprague-Dawley rats were used. Polyethylene catheters were implanted into the bladder to record the intravesical pressure (IVP) and into the femoral artery to administer medication. A balloon-fitted catheter was positioned in the abdominal cavity to record the IAP. Awake cystometries were performed before and after intraarterial administration of propiverine 1 mg/kg (n=6), intravesical administration of 50microM PGE2 only (n=6), or intravesical PGE2 plus 1 mg/kg (n=4) or 3 mg/kg (n=6) of intraarterial propiverine. Cystometric pressure and volume parameters and variables related to detrusor overactivity (DO) were investigated. RESULTS: Rats administered intravesical PGE2 showed increased pressure parameters and decreased volume parameters comparable to the DO model, which was effectively prevented by propiverine (1 or 3 mg/kg). Typical DO shown during the filling phase was decreased by intraarterial propiverine (3 mg/kg) injection. After propiverine (3 mg/kg) injection, IAP was increased at the time of micturition pressure with or without threshold pressure (p<0.05, p<0.01) depending on the dose administered. CONCLUSIONS: Propiverine improved pressure- and volume-related parameters in an OAB model. Furthermore, it also decreased the frequency of DO. However, higher concentrations of propiverine induced straining voiding.

Efficacy and Safety of Propiverine Hydrochloride 40mg in Treatment of Overactive Bladder : Prospective, Multicenter, Observational study

PURPOSE: This study aims to compare the efficacy and safety of propiverine hydrochloride (propiverine) 40mg for the treatment of overactive bladder (OAB). MATERIAL AND METHODS: Total of 284 patients (male:86, female:198) with OAB were included in this study. The patients were treated with propiverine 20mg twice daily or 40mg once daily for 8 weeks. The initial evaluation included with history taking, physical examination, International Prostatic Symptom Score (IPSS), IPSS QoL and consecutive voiding diaries for 3 days. After a 8-week treatment, IPSS, IPSS QoL, patients perception of treatment benefit, global assessment of efficacy by physicain and safety were evaluated. RESULTS: Two hundred eighteen patients were treated with propiverine 20mg twice daily and 66 patients treated with 40mg once daily. The 59 patients had been treated previously with anticholinergics. After a 8-week treatment, IPSS score (total, voiding and storage subscore) and IPSS QoL were improved in all patients (p<0.05). After a 8-week with propiverine 40mg once daily, improvement of IPSS score was noted in the patients non-responsive to anticholinergics previously (p<0.05). The patients treated with propiverine 40mg once daily showed much more symptomatic improvements assessed by physicians than 20mg twice daily (p<0.05). The overall side effect was noted in the 13.4% patients and the most common side effect was dry mouth. CONCLUSION: Propiverine 40mg once daily is considered to reduce the symptom of OAB effectively and can be used safely in the patients with OAB. Treatment with propiverine 40mg is seemed to show more improvement in the unsatisfactory patients with previous anticholinergics.

Changes in Overactive Bladder Symptoms after Discontinuation of a Successful Treatment with Antimuscarinic Agent: A Prospective Trial / 대한비뇨기과학회지

PURPOSE: To prospectively investigated the symptom changes in women with an overactive bladder (OAB) after discontinuation of 3 months of successful treatment with antimuscarinics and the pre-treatment factors that contributed to retreatment. MATERIALS AND METHODS: Sixty-eight women (mean age 51.4 years) with improvement in the symptoms of OAB after 4 weeks of treatment with propiverine hydrochloride (20mg/day) were prospectively enrolled in a protocol consisting of 8 further weeks of medication and a 4-week period of discontinuation. The frequency-volume charts were assessed before treatment, after the 12 weeks of therapy, and 4 weeks the end of the therapy. Changes in the frequencies, nocturia, urgency scores and urge incontinence at 12 and 16 weeks were evaluated. RESULTS: All of the OAB symptoms 4 weeks after discontinuation of medication remained improved compared to those initially recorded, but then deteriorated during further medication. At the baseline, and 12 and 16 weeks, the mean frequencies, nocturia and urgency scores per day were 11.2, 7.3 and 8.3, 1.6, 0.4 and 0.8, and 1.7, 0.6 and 1.2, respectively. The retreatment rate was 35.3%. Patients in the retreatment group were older (58.8 vs. 47.3 years, p<0.001) and had higher initial urgency scores (1.9 vs. 1.6, p=0.034). In an urodynamic study of 23 patients, those without detrusor overactivity (DO) maintained a significantly improved frequency after cessation of mediation, whereas those with DO (60.9%) did not. The retreatment rate was higher in patients with DO, but the difference was not significant. CONCLUSIONS: Three months of antimuscarinic therapy for OAB may not be sufficient. Older patients, or those with severe urgency, may be more likely to return to treatment.

The Effects of Combined Therapy with Propiverine (BUP-4(R)) after alpha-blocker on the Improvements of Quality of Life Scores in Patients with Benign Prostatic Hyperplasia Accompaniedwith Overactive Bladder / 대한비뇨기과학회지

PURPOSE: The aim of this study was to estimate the effects of the combination therapy of alpha-blocker and propiverine on the quality of life (QoL) scores of patients with benign prostatic hyperplasia (BPH) accompanied with an overactive bladder. MATERIALS AND METHODS: One hundred and twenty-six patients, aged between 50 to 80 years old, with BPH were included in this study. They were evaluated by their International Prostate Symptom Scores (IPSS) and QoL questionnaires, DRE, transrectal ultrasound, uroflowmetry and residual urine checks and urine analysis. 3 months of alpha-blocker (tamsulosin 0.2mg/day) treatment was performed on all the patients, but 29 complained of persistent irritative symptoms. After re-examinations, they were treated with the alpha-blocker combined with propiverine (20mg/day) therapy for 2 months. RESULTS: The mean age of the patients who complained of irritative voiding symptoms was 66.7 years, ranging from 52 to 79 years old. Before the treatment, their IPSS, QoL score, voiding volume, peak flow rate (Qmax) and post-voiding residual urine volume (PVR) were 20.1+/-4.7, 4.2+/-0.7, 211.3+/-59.4ml, 9.7+/-1.3ml/s and 51.5+/-26.5ml, respectively. After the alpha-blocker therapy, the results were 13.5+/-3.5, 3.3+/-0.5, 281.1+/-67.6ml, 14.7+/-2.7ml/s and 16.5+/-13.1ml; whereas, after the combination therapy with propiverine they were, 10.8+/-3.7, 2.1+/-0.5, 315.7+/-69.7ml, 14.5+/-2.7ml/s and 29.6+/-15.8ml, respectively. The IPSS, QoL score and voiding volume improved significantly when they were treated with the combination therapy compared with just the alpha- blocker therapy. The changes in the Qmax and PVR showed no significant difference. CONCLUSIONS: In carefully selected BPH patients, accompanied with an overactive bladder, the combination therapy of propiverine after alpha-blocker should improve the patient's satisfaction and the QoL scores.

The Clinical Effects of Amitriptyline in Patients with Urinary Frequency and Chronic Pelvic Pain Syndrome / 대한비뇨기과학회지

PURPOSE: We evaluated the effects of amitriptyline in patients with urinary frequency or pelvic pain syndrome and compared with propiverine hydrochloride (BUP-4(R)) and diazepam (Valium(R)). MATERIALS AND METHODS: One-hundred and sixty-eight patients with urinary frequency or pain were included and 38 out of 168 patients were lost to follow up. The patients with interstitial cystitis, UTI and neurogenic bladder were excluded. Amitriptyline group were instructed to take 25mg to 75mg of amitriptyline before bed. Propiverine hy drochloride and diazepam group were instructed to take 20mg, 4-6mg before bed, respectively. The clinical effects and side effects were evaluated after 4 weeks of medication. RESULTS: In the amitriptyline group, 73.1% in 78 patients with frequency, 68.3% in 60 pain, 65.6% in 32 nocturia, 53.8% in 26 weak urinary stream, 53.8% in 13 dysuria, 72.7% in 11 urgency showed symptom improvement. Urinary frequency and pain score were significantly decreased in the amitriptyline group. In the propiverine hydrochloride group, 66.7% in 21 patients with frequency, 38.8% in 18 pain showed symptom improvement. In the diazepam group, 37.5% in 24 patients with frequency, 31.3% in 16 pain showed symptom improvement. Side effects of amitriptyline had appeared in 24 (27.6%) out of 87 patients; 17 cases of dry mouth, 10 drowsiness, 2 agitation, 2 nausea, 1 constipation and 1 skin rash. CONCLUSIONS: Amitriptyline is useful in vague voiding symptoms especially in urinary frequency and chronic pelvic pain syndrome. It is equally effective in both men and women. Side effects are minimal and tolerable. A double-blind placebo-controlled trial is necessary for general acceptance in the future.

Clinical and Urodynamic Effects of Propiverine Hydrochloride for Neurogenic Bladder Patient with Urinary Frequency and Incontinence / 대한비뇨기과학회지

PURPOSE: Patients with neurogenic bladder ultimately undergo morphometric and functional changes of their bladder and urethra. As a result, voiding symptoms such as frequency, nocturia, urgency and incontinence appear Propiverine hydrochloride(BUP-4) is a benzylic acid derivative with musculotropic antispamodic activity and moderate anticholinergic effect. We evaluated the clinical and urodynamic effects of BUP-4 for patients with neurogenic urinary frequency and incontinence MATERIALS AND METHODS: Twenty six patients with neurogenic bladder suffering from urinary frequency and incontinence(including 5 placebo) were given 20mg of BUP-4 orally a day and its clinical and urodynamic effect were evaluated. RESULTS: In the group treated with BUP-4 for four weeks, 57.9% in 19 patients with frequency, 53.3% in 15 nocturia, 50.0% in 14 weak stream, 55.6% in 9 intermittency, 50.0% in 10 dribbling, 64.3% in 14 urgency, 55.6% in 9 hesitancy, 73.7% in 19 incontinence showed improvement of their symptom. Urodynamic study performed after treatment with BUP-4 for 4 weeks or more revealed greater than 10% increase in bladder capacity compared to pretreatment study in 11 patients out of 21(52.4%) and their maximum bladder capacity increased significantly from 181.7+/-101.3 to 249.4+/- 184.7mL(p=0.012). Maximum detrusor pressure decreased from 52.5+/-35.6 to 50.9+/- 26.8cmH2O(p=0.010). Changes in compliance and volume on the first urge sense were statistically insignificant. In placebo group, no significant symptomatic and urodynamic improvement were reported. Side effects of the drug had appeared in 7 patients(33.3%) out of 21 after 4 weeks of treatment -5 cases of dry mouth and 2 cases of nausea - but they were not severe enough to stop the treatment. CONCLUSIONS: The use of BUP-4 in patients with neurogenic bladder results in improvement of symptoms and urodynamic profile(bladder capacity and maximum detrusor pressure). Thus, BUP-4 could be used as one of the first line drugs in the treatment of patients with neurogenic bladder.

Inhibitory Effects of Tiropramide and Propiverine HCI against Smooth Muscle Contraction of Rat Urinary Bladder: In-vitro Muscle Strip Study / 대한비뇨기과학회지

AIMS OF STUDY: Present study designed to observe inhibitory effects of propiverine HC1 and tiropramide against the smooth muscle contraction of female rat bladder. Propiverine has both direct smooth muscle relaxation and anticholinergic effect and has relatively fewer side effect than conventionally used drugs such as oxybutinin. Tiropramide has been known as modulatory agents of gastrointestinal motility but also has inhibitory effects against the bladder contraction. METHODS: 30 adult female Sprague-Dawley rats were used. Bladder body above ureteral orifice was resected under pentobarbital anesthesia. 1 x 0.5 cm sized smooth muscle strip was made, and incubated in Tyrode`s solution aerated with 95% oxygen. After reaching equilibrium state, each strip was stimulated by field stimulation (FS, 1-32 Hz) and bethanechol administration (0.0000001-0.0001M). From each strip, degree of muscle contraction was recorded by physiograph (Gilson IC-MP). After the control stimulations, each strip was treated by atropine, tiropramide, oxybutinin and propiverine HC1. After 30 minutes, same stimulation were repeated and degree of muscle contraction was compared to pre incubation data. RESULTS: Frequency and dose dependent muscle contractions were noted for both FS and bethanechol stimulation. Greater degree of contractions were noted for FS than for bethanechol stimulation. Inhibitory effects of tiropramide, propiverine HC1 and oxybutinin were greater than those of atropine at FS (1-32 Hz). At high concentration (0.0001M), all of the drugs but atropine inhibited field stimulated smooth muscle contraction more than 90%. At lower concentration (0. 0000001-0.000001M), inhibitory actions of oxybutinin and propiverine HC1 were greater than that of tiropramide (p>0.05). Propiverine HC1 and oxybutinin had similar inhibitory effect for all con-centration. At higher concentration (0.0001M), inhibitory effects of tiro-pramide were more than 98% whereas those of oxybutinin and propiverine HC1 were 88%. At low concentration (0.0000001-0.000001M), oxybutinin exhibited greater inhibition against the bethanechol induced contraction than did tiropramide and propiverine HC1. With these results, it was suggested that in low concentration, oxybutinin and propiverine HCI had greater inhibitory effect than did tiropramide against smooth muscle contraction of the bladder. In high concentration though, tiropramide had superior inhibitory effect than did oxybutinin and propiverine HC1. Since, no difference was noted between oxybutinin and propiverine HC1 for the inhibitory action of bladder contraction, propiverine HC1 seems reasonable substitute for the treatment of detrusor hyperreflexia with less side effects. Also these results indicate that tiropramide can be used for the management of unstable bladder.