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SOLIFENACIN IN MULTIPLE SCLEROSIS PATIENTS WITH OVERACTIVE BLADDER – A PROSPECTIVE STUDY
1101
1102
THE PRESENCE AND THE FUNCTIONAL ROLE OF MUSCARINIC RECEPTOR SUBTYPES IN HUMAN BLADDER SMOOTH MUSCLE IN PATIENTS WITH NORMAL AND DETRUSOR OVERACTIVITY
JUVENILE PIG DETRUSOR DIFFERS IN CONTRACTILE MECHANISMS FROM MATURE TISSUE
Yamanishi T., Mizuno T., Abe H., Kamai T., Arai K., Yoshida K.I.
1
Wuest M.1, Schlobach Da Costa K.1, Hecht J.1, Christ T.1, Braeter M.2, Ravens U.1 Medical Faculty, Dresden University of Technology, Dept. of Pharmacology and Toxicology, Dresden, Germany, 2Apogepha Arzneimittel GmbH, Medical Sciences, Dresden, Germany
Dokkyo University, Urology, Tochigi, Japan INTRODUCTION & OBJECTIVES: The aim of the present study is to compare the mRNA expression of MR subtypes and the affinities of various muscarinic antagonists against carbachol-induced contraction in human detrusor muscles between normal state and detrusor overactivity. MATERIAL & METHODS: Tissue samples of human bladder muscles were obtained from patients undergoing total cystectomy due to bladder cancer (normal bladder), and those undergoing augmentation cystoplasty due to neurogenic bladder dysfunction (detrusor overactivity). The presence of detrusor overactivity was proven in video-urodynamic studies or ambulatory urodynamics before the surgery. The expression of mRNA for M1-M5 MR subtypes was evaluated by real-time RT-PCR using ABI PRISM 7700. Tissues were mounted in 5 ml organ baths containing Krebs solution, and concentration-response curves (CRCs) to carbachol were obtained. After incubation for 30 minutes, a second CRC to carbachol was constructed in the continued presence of antagonist or vehicle. In this way, 4 CRCs to carbachol were obtained from the same strip, three in the presence of increasing concentrations of 4DAMP (3,10,30nM), methoctramine (1,3 and 10μM), pirenzepine(1,3 and 10μM), trospium, tolterodine, propiverine, oxybutynin (3,10,30nM) or in the presence of vehicle. RESULTS: The mean expression of mRNA for M1, M2, M3, M4 and M5 MR subtypes accounted for 33%, 22%, 24% 11%, 10%, respectively of the overall MRs. However, the data were various among the individuals. Carbachol produced concentration-dependent contraction of the normal human urinary bladder with mean pEC50 values and maximum responses of 6.51±0.14 and 6.81±0.79 g, respectively. Carbachol produced concentration-dependent contraction of the human urinary bladder with detrusor overactivity with mean pEC50 values and maximum responses of 6.36±0.13 and 9.90±1.04g, respectively. All muscarinic antagonists produced parallel, rightward displacement of the CRCs to carbachol without affecting maximum responses. Mean (±SEM) pA2 values in normal and detrusor overactivity, respectively, were 9.87±0.09 and 9.01±0.12 for 4-DAMP, 6.64±0.05 and 6.18±0.09 for methoctramine, 7.38±0.09 and 7.33±0.11 for pirenzepine, 9.78±0.11 and 9.71±0.64 for trospium, 9.11±0.17 and 8.70±0.16 for tolterodine, 7.92±0.20 and 8.30±0.11 for propiverine, and 8.17±0.10 and 8.39±0.92 for oxybutynin. CONCLUSIONS: M3-receptors mainly mediate contractions in normal human bladder. Antagonist affinities of muscarinic antagonists did not change in bladder strips with detrusor overactivity, indicating that M3-receptors still mediate contractions in this condition.
INTRODUCTION & OBJECTIVES: The atropine-resistant component of contraction is larger in juvenile than in mature detrusor suggesting that contractions induced by other neurotransmitters like ATP and noradrenaline are regulated during maturation. In juvenile detrusor little is known about adenosine-mediated relaxation or the effects of the spasmolytic drug propiverine. Here we have examined effects of atropine and adenosine in juvenile and mature pig detrusor in order to detect possible differences in contractile mechanisms. L-type calcium currents (ICa,L)which strongly influences pig detrusor contraction were studied as well. MATERIAL & METHODS: Mucosa and serosa were removed from urinary bladders of juvenile (8-12 weeks; 12 to 35kg body weight) and mature pigs (>40 weeks; >100kg). Contractions were measured in response to electric field stimulation (EFS; 1ms pulses, 90mA, 30Hz). ICa,L was measured in freshly isolated detrusor smooth muscle cells (DSMC) using standard whole-cell patch-clamp technique at room temperature with 3.8mM BaCl2 as charge carrier. RESULTS: The amplitudes of EFS–induced contractions were similar in juvenile and adult pigs: 0.94±0.16 mN/mg wet weight (w.w.; n=17) and 0.79±0.11 mN/mg w.w. (n=26, n.s.) The non-selective muscarinic receptor antagonist atropine (10μM) reduced EFS to 42±8% of control (n=5) in juvenile, to about 20% in adult tissue. We confirm that potency of atropine was significantly higher in juvenile than in mature pigs (-log IC50 [M]: 8.49±0.14 versus 7.82±0.08, p<0.001). Efficacy of exogenously added adenosine tended to be higher in juvenile than in mature detrusor (remaining contraction 25±6% of pre-drug control, n=4 vs. 40±7%, n=6, p>0.05), whereas potency was not different. In juvenile tissue addition of 3mM adenosine on top of atropine completely suppressed the atropine-resistant component. Contractions were similarly depressed when 10μM atropine was added on top of adenosine. No further reduction occurred with the neurotoxin tetrodotoxin (1μM). The spasmolytic drug propiverine fully depressed EFS contractions with similar potency in juvenile and mature detrusor. In juvenile DSMC ICa,L was significantly smaller than in mature cells (1.19±0.12 pA/pF, n=7/3 vs. 0.83±0.09 pA/pF, n=7/3, p<0.05). Propiverine completely blocked ICa,L in both groups albeit with lesser potency in juvenile than in mature cells (log IC50 [M]: 4.70±0.10 vs. 6.49±0.04). CONCLUSIONS: We have shown that non-cholinergic contractions are smaller, adenosinemediated relaxation tends to be larger and ICa,L amplitude is smaller but less sensitive to propiverine in juvenile than in mature pig detrusor. These results suggest that contractile mechanisms in pig detrusor change with age, but effects of the spasmolytic drug propiverine on detrusor contraction are not affected.
1103
1104
WITH
ARE EFFICACY AND TOLERABILITY OF PROPIVERINE AND OXYBUTYNIN COMPARABLE IN CHILDREN WITH NEUROGENIC DETRUSOR OVERACTIVITY (NDO)? A MULTICENTRE OBSERVATIONAL COHORT STUDY
INTRODUCTION & OBJECTIVES: The efficacy and safety of Solifenacin for the treatment of the overactive bladder (OAB) has already been demonstrated. An underlying neurological disease was an exclusion criterion in the clinical studies performed until now, so no decree can be made on its efficacy in a multiple sclerosis (MS) patient population. In this prospective study the efficacy of Solifenacin was investigated in a MS patient population with complaints of OAB.
Madersbacher H.1, Muertz G.2, Alloussi S.3, Beute M.4, Buerst M.5, Domurath B.6, Henne T.7, Koerner I.8, Niedeggen A.9, Nounla J.10, Pannek J.11, Schuldt M.12, Schulte-Baukloh H.13, Schultz-Lampel D.14, Siemer S.15, Stuckert T.16, Willer B.14, Bock P.17, Hanisch J.17
SOLIFENACIN IN MULTIPLE SCLEROSIS PATIENTS OVERACTIVE BLADDER – A PROSPECTIVE STUDY Van Rey F., Heesakkers J. The Radboud University Medical Centre, Urology, Nijmegen, The Netherlands
MATERIAL & METHODS: 30 Patients with MS with complaints of OAB were treated with Solifenacin 5 mg once daily for a period of 4 weeks. Afterwards, in case of acceptable or no side effects and subjective insufficient efficacy, patients could raise the daily dosage to 10 mg. After a total treatment period of 8 weeks the efficacy of Solifenacin was evaluated. Evaluation was done by means of a 72-hour voiding diary and a MS specific quality of life questionnaire (MS QoL 54). Primary endpoints were defined as change from baseline in mean number of micturition per 24 hours, change from baseline in mean voided volume per void, number of incontinence episodes per day and number of pads used per day. Change in MS 54 QoL was a secondary endpoint. RESULTS: 30 MS patients (12 male, 18 female) entered the study, between January 2005 and July 2005. After 4 weeks of treatment with Solifenacin 5 mg, 28 patients reported acceptable or no side effects. of these patients 17 continued the study with the 10mg dosage, 11 stayed on 5 mg. 2 patients withdrew from the study due to side effects (gastro-intestinal and skin rash). Evaluation after 8 weeks of treatment compared to baseline showed a decrease on all primary endpoints (see table). 22 out of 28 patients chose to continue therapy after termination of the study. In spite of the fact that many patients reported a subjective improvement on QoL, this wasn’t apparent when analysing the MS QoL 54. We hypothesize that the little change in QoL is due to the small sample size or because only one question about LUTS is incorporated in the MS QoL 54.
Baseline (IQD)
After 8 weeks of treatment (IQD)
Wilcoxon Signed Ranks Test
1
Universityhospital of Innsbruck, Neurourogical Unit, Innsbruck, Austria, 2Apogepha Arzneimittel GmbH, Department of Urology, Dresden, Germany, 3Städtisches Klinikum Neunkirchen, Urologische Abteilung, Neunkirchen, Germany, 4 Allgemeines Krankenhaus Hamburg, Urology, Hamburg, Germany, 5Kliniken des Landkreises Deggendorf, Klinik Für Urologie und Kinderurologie, Deggendorf, Germany, 6Werner Wicker Klinik, Urologische Abteilung, Bad Wildungen, Germany, 7Altonaer Kinderkrankenhaus, Urologische Abteilung, Hamburg, Germany, 8Universitätsklinikum Essen, Klinik und Poliklinik Für Urologie, Essen, Germany, 9Unfallkrankenhaus, Urologische Abteilung, Berlin, Germany, 10 Universität Leipzig, Klinik und Poliklinik Für Kinderchirurgie, Leipzig, Germany, 11Marienhospital Herne, Urology, Herne, Germany, 12Ernst-Moritz-Arndt-Universität, Klinik und Poliklinik für Kinderchirurgie, Greifswald, Germany, 13St. Hedwig-Krankenhaus, Urologische Abteilung, Berlin, Germany, 14Klinikum Villingen-Schwenningen, Kontinenzzentrum Südwest, Villingen-Schwenningen, Germany, 15Unikliniken Des Saarlandes, Klinik für Urologie und Kinderurologie, Homburg, Germany, 16Heinrich-Braun-Krankenhaus, Klinik für Kinder- Und Jugendmedizin, Zwickau, Germany, 17IFAG, Urology, Basel, Switzerland INTRODUCTION & OBJECTIVES: This study assesses efficacy and tolerability of propiverine and oxybutynin comparatively in children with NDO aged 1–18 years, which are usually treated with antimuscarinics and intermittent catheterisation. MATERIAL & METHODS: Altogether 255 children with NDO (199 myelomeningocele (MMC), 46 spinal cord injury, 10 different diagnoses; 127 propiverine, 128 oxybutynin) were evaluated retrospectively at 14 centres. RESULTS: Maximum detrusor pressure (pdet), the clinically most relevant efficacy outcome parameter due to its prognostic implications, was on average significantly reduced in both treatment groups. The results favoured propiverine significantly (tab. 1). Individual reductions of pdet were assumed to be successful either if values below 40 cm H20 or if a reduction of at least 50% compared to pre-treatment values resulted: 74% of the propiverine group compared to 50% of the oxybutynin group achieved these primary outcome criteria. Results of other parameters are given in table 1. Table 1: Urodynamic and clinical parameters Propiverine
Max. detrusor pressure (cm H20)
Oxybutynin
pre
post
pre
post
59.8
36.7
65.2
54.9
Median frequency/day
11.7 (9.3-13.4)
9.5 (6.9-10.9)
p=0.000
Compliance (ml/cm H20)
18.94
27.56
9.99
15.64
Median voided volume/void
121.9 (103.1-152.9)
155.3 (103.1-198.2)
p=0.000
Max. bladder capacity (ml)
145.93
242.28
221.82
309.97
Median incontinence episodes/day
1.3 (0.0-2.7)
0.2 (0.0-1.7)
p=0.360
Continence (%)
7.69
31.62
20.80
50.41
Median no. pads used/day
2.0 (0.0-3.4)
1.0 (0.0-2.0)
p=0.010
Dosage (mg)
16.72
20.89
9.75
13.59
Mean MS QoL 54 (total)
Baseline (SD)
8 weeks (SD)
Paired T-Test
113.1 (30.9)
116.1 (30.9)
p=0.955
CONCLUSIONS: Solifenacin is effective in the treatment of MS patients with complaints of a neurogenic overactive bladder. Both on complaints of urgency frequency and urge incontinence significant improvements were observed. The MS QoL 54 is not sensitive enough to detect changes in lower urinary tract functioning in MS patients.
Eur Urol Suppl 2006;5(2):298
Propiverine was better tolerated than oxybutynin in the total study population (9.40% versus 17.46% adverse events overall). No serious adverse events occurred. Oxybutynin had to be used in dosages twice as high as recommended to achieve the goals, whereas propiverine was administered in dosages lower than recommended. CONCLUSIONS: Despite statistical superiority of propiverine efficacy results have to be discussed with precaution: urodynamic baseline values of both groups differ, urodynamic curves (e.g. compliance) might have been interpreted different at 14 study centres, and heterogenity of patients must be considered. The significantly more effective treatment response of propiverine compared to oxybutynin in the total population was due to an enhanced response of MMCchildren to propiverine, which might be due to the additional calcium-channel-modulating effects of propiverine. The superior tolerability profile of propiverine compared to oxybutynin was confirmed also in children with NDO.
1102
THE PRESENCE AND THE FUNCTIONAL ROLE OF MUSCARINIC RECEPTOR SUBTYPES IN HUMAN BLADDER SMOOTH MUSCLE IN PATIENTS WITH NORMAL AND DETRUSOR OVERACTIVITY
JUVENILE PIG DETRUSOR DIFFERS IN CONTRACTILE MECHANISMS FROM MATURE TISSUE
Yamanishi T., Mizuno T., Abe H., Kamai T., Arai K., Yoshida K.I.
1
Wuest M.1, Schlobach Da Costa K.1, Hecht J.1, Christ T.1, Braeter M.2, Ravens U.1 Medical Faculty, Dresden University of Technology, Dept. of Pharmacology and Toxicology, Dresden, Germany, 2Apogepha Arzneimittel GmbH, Medical Sciences, Dresden, Germany
Dokkyo University, Urology, Tochigi, Japan INTRODUCTION & OBJECTIVES: The aim of the present study is to compare the mRNA expression of MR subtypes and the affinities of various muscarinic antagonists against carbachol-induced contraction in human detrusor muscles between normal state and detrusor overactivity. MATERIAL & METHODS: Tissue samples of human bladder muscles were obtained from patients undergoing total cystectomy due to bladder cancer (normal bladder), and those undergoing augmentation cystoplasty due to neurogenic bladder dysfunction (detrusor overactivity). The presence of detrusor overactivity was proven in video-urodynamic studies or ambulatory urodynamics before the surgery. The expression of mRNA for M1-M5 MR subtypes was evaluated by real-time RT-PCR using ABI PRISM 7700. Tissues were mounted in 5 ml organ baths containing Krebs solution, and concentration-response curves (CRCs) to carbachol were obtained. After incubation for 30 minutes, a second CRC to carbachol was constructed in the continued presence of antagonist or vehicle. In this way, 4 CRCs to carbachol were obtained from the same strip, three in the presence of increasing concentrations of 4DAMP (3,10,30nM), methoctramine (1,3 and 10μM), pirenzepine(1,3 and 10μM), trospium, tolterodine, propiverine, oxybutynin (3,10,30nM) or in the presence of vehicle. RESULTS: The mean expression of mRNA for M1, M2, M3, M4 and M5 MR subtypes accounted for 33%, 22%, 24% 11%, 10%, respectively of the overall MRs. However, the data were various among the individuals. Carbachol produced concentration-dependent contraction of the normal human urinary bladder with mean pEC50 values and maximum responses of 6.51±0.14 and 6.81±0.79 g, respectively. Carbachol produced concentration-dependent contraction of the human urinary bladder with detrusor overactivity with mean pEC50 values and maximum responses of 6.36±0.13 and 9.90±1.04g, respectively. All muscarinic antagonists produced parallel, rightward displacement of the CRCs to carbachol without affecting maximum responses. Mean (±SEM) pA2 values in normal and detrusor overactivity, respectively, were 9.87±0.09 and 9.01±0.12 for 4-DAMP, 6.64±0.05 and 6.18±0.09 for methoctramine, 7.38±0.09 and 7.33±0.11 for pirenzepine, 9.78±0.11 and 9.71±0.64 for trospium, 9.11±0.17 and 8.70±0.16 for tolterodine, 7.92±0.20 and 8.30±0.11 for propiverine, and 8.17±0.10 and 8.39±0.92 for oxybutynin. CONCLUSIONS: M3-receptors mainly mediate contractions in normal human bladder. Antagonist affinities of muscarinic antagonists did not change in bladder strips with detrusor overactivity, indicating that M3-receptors still mediate contractions in this condition.
INTRODUCTION & OBJECTIVES: The atropine-resistant component of contraction is larger in juvenile than in mature detrusor suggesting that contractions induced by other neurotransmitters like ATP and noradrenaline are regulated during maturation. In juvenile detrusor little is known about adenosine-mediated relaxation or the effects of the spasmolytic drug propiverine. Here we have examined effects of atropine and adenosine in juvenile and mature pig detrusor in order to detect possible differences in contractile mechanisms. L-type calcium currents (ICa,L)which strongly influences pig detrusor contraction were studied as well. MATERIAL & METHODS: Mucosa and serosa were removed from urinary bladders of juvenile (8-12 weeks; 12 to 35kg body weight) and mature pigs (>40 weeks; >100kg). Contractions were measured in response to electric field stimulation (EFS; 1ms pulses, 90mA, 30Hz). ICa,L was measured in freshly isolated detrusor smooth muscle cells (DSMC) using standard whole-cell patch-clamp technique at room temperature with 3.8mM BaCl2 as charge carrier. RESULTS: The amplitudes of EFS–induced contractions were similar in juvenile and adult pigs: 0.94±0.16 mN/mg wet weight (w.w.; n=17) and 0.79±0.11 mN/mg w.w. (n=26, n.s.) The non-selective muscarinic receptor antagonist atropine (10μM) reduced EFS to 42±8% of control (n=5) in juvenile, to about 20% in adult tissue. We confirm that potency of atropine was significantly higher in juvenile than in mature pigs (-log IC50 [M]: 8.49±0.14 versus 7.82±0.08, p<0.001). Efficacy of exogenously added adenosine tended to be higher in juvenile than in mature detrusor (remaining contraction 25±6% of pre-drug control, n=4 vs. 40±7%, n=6, p>0.05), whereas potency was not different. In juvenile tissue addition of 3mM adenosine on top of atropine completely suppressed the atropine-resistant component. Contractions were similarly depressed when 10μM atropine was added on top of adenosine. No further reduction occurred with the neurotoxin tetrodotoxin (1μM). The spasmolytic drug propiverine fully depressed EFS contractions with similar potency in juvenile and mature detrusor. In juvenile DSMC ICa,L was significantly smaller than in mature cells (1.19±0.12 pA/pF, n=7/3 vs. 0.83±0.09 pA/pF, n=7/3, p<0.05). Propiverine completely blocked ICa,L in both groups albeit with lesser potency in juvenile than in mature cells (log IC50 [M]: 4.70±0.10 vs. 6.49±0.04). CONCLUSIONS: We have shown that non-cholinergic contractions are smaller, adenosinemediated relaxation tends to be larger and ICa,L amplitude is smaller but less sensitive to propiverine in juvenile than in mature pig detrusor. These results suggest that contractile mechanisms in pig detrusor change with age, but effects of the spasmolytic drug propiverine on detrusor contraction are not affected.
1103
1104
WITH
ARE EFFICACY AND TOLERABILITY OF PROPIVERINE AND OXYBUTYNIN COMPARABLE IN CHILDREN WITH NEUROGENIC DETRUSOR OVERACTIVITY (NDO)? A MULTICENTRE OBSERVATIONAL COHORT STUDY
INTRODUCTION & OBJECTIVES: The efficacy and safety of Solifenacin for the treatment of the overactive bladder (OAB) has already been demonstrated. An underlying neurological disease was an exclusion criterion in the clinical studies performed until now, so no decree can be made on its efficacy in a multiple sclerosis (MS) patient population. In this prospective study the efficacy of Solifenacin was investigated in a MS patient population with complaints of OAB.
Madersbacher H.1, Muertz G.2, Alloussi S.3, Beute M.4, Buerst M.5, Domurath B.6, Henne T.7, Koerner I.8, Niedeggen A.9, Nounla J.10, Pannek J.11, Schuldt M.12, Schulte-Baukloh H.13, Schultz-Lampel D.14, Siemer S.15, Stuckert T.16, Willer B.14, Bock P.17, Hanisch J.17
SOLIFENACIN IN MULTIPLE SCLEROSIS PATIENTS OVERACTIVE BLADDER – A PROSPECTIVE STUDY Van Rey F., Heesakkers J. The Radboud University Medical Centre, Urology, Nijmegen, The Netherlands
MATERIAL & METHODS: 30 Patients with MS with complaints of OAB were treated with Solifenacin 5 mg once daily for a period of 4 weeks. Afterwards, in case of acceptable or no side effects and subjective insufficient efficacy, patients could raise the daily dosage to 10 mg. After a total treatment period of 8 weeks the efficacy of Solifenacin was evaluated. Evaluation was done by means of a 72-hour voiding diary and a MS specific quality of life questionnaire (MS QoL 54). Primary endpoints were defined as change from baseline in mean number of micturition per 24 hours, change from baseline in mean voided volume per void, number of incontinence episodes per day and number of pads used per day. Change in MS 54 QoL was a secondary endpoint. RESULTS: 30 MS patients (12 male, 18 female) entered the study, between January 2005 and July 2005. After 4 weeks of treatment with Solifenacin 5 mg, 28 patients reported acceptable or no side effects. of these patients 17 continued the study with the 10mg dosage, 11 stayed on 5 mg. 2 patients withdrew from the study due to side effects (gastro-intestinal and skin rash). Evaluation after 8 weeks of treatment compared to baseline showed a decrease on all primary endpoints (see table). 22 out of 28 patients chose to continue therapy after termination of the study. In spite of the fact that many patients reported a subjective improvement on QoL, this wasn’t apparent when analysing the MS QoL 54. We hypothesize that the little change in QoL is due to the small sample size or because only one question about LUTS is incorporated in the MS QoL 54.
Baseline (IQD)
After 8 weeks of treatment (IQD)
Wilcoxon Signed Ranks Test
1
Universityhospital of Innsbruck, Neurourogical Unit, Innsbruck, Austria, 2Apogepha Arzneimittel GmbH, Department of Urology, Dresden, Germany, 3Städtisches Klinikum Neunkirchen, Urologische Abteilung, Neunkirchen, Germany, 4 Allgemeines Krankenhaus Hamburg, Urology, Hamburg, Germany, 5Kliniken des Landkreises Deggendorf, Klinik Für Urologie und Kinderurologie, Deggendorf, Germany, 6Werner Wicker Klinik, Urologische Abteilung, Bad Wildungen, Germany, 7Altonaer Kinderkrankenhaus, Urologische Abteilung, Hamburg, Germany, 8Universitätsklinikum Essen, Klinik und Poliklinik Für Urologie, Essen, Germany, 9Unfallkrankenhaus, Urologische Abteilung, Berlin, Germany, 10 Universität Leipzig, Klinik und Poliklinik Für Kinderchirurgie, Leipzig, Germany, 11Marienhospital Herne, Urology, Herne, Germany, 12Ernst-Moritz-Arndt-Universität, Klinik und Poliklinik für Kinderchirurgie, Greifswald, Germany, 13St. Hedwig-Krankenhaus, Urologische Abteilung, Berlin, Germany, 14Klinikum Villingen-Schwenningen, Kontinenzzentrum Südwest, Villingen-Schwenningen, Germany, 15Unikliniken Des Saarlandes, Klinik für Urologie und Kinderurologie, Homburg, Germany, 16Heinrich-Braun-Krankenhaus, Klinik für Kinder- Und Jugendmedizin, Zwickau, Germany, 17IFAG, Urology, Basel, Switzerland INTRODUCTION & OBJECTIVES: This study assesses efficacy and tolerability of propiverine and oxybutynin comparatively in children with NDO aged 1–18 years, which are usually treated with antimuscarinics and intermittent catheterisation. MATERIAL & METHODS: Altogether 255 children with NDO (199 myelomeningocele (MMC), 46 spinal cord injury, 10 different diagnoses; 127 propiverine, 128 oxybutynin) were evaluated retrospectively at 14 centres. RESULTS: Maximum detrusor pressure (pdet), the clinically most relevant efficacy outcome parameter due to its prognostic implications, was on average significantly reduced in both treatment groups. The results favoured propiverine significantly (tab. 1). Individual reductions of pdet were assumed to be successful either if values below 40 cm H20 or if a reduction of at least 50% compared to pre-treatment values resulted: 74% of the propiverine group compared to 50% of the oxybutynin group achieved these primary outcome criteria. Results of other parameters are given in table 1. Table 1: Urodynamic and clinical parameters Propiverine
Max. detrusor pressure (cm H20)
Oxybutynin
pre
post
pre
post
59.8
36.7
65.2
54.9
Median frequency/day
11.7 (9.3-13.4)
9.5 (6.9-10.9)
p=0.000
Compliance (ml/cm H20)
18.94
27.56
9.99
15.64
Median voided volume/void
121.9 (103.1-152.9)
155.3 (103.1-198.2)
p=0.000
Max. bladder capacity (ml)
145.93
242.28
221.82
309.97
Median incontinence episodes/day
1.3 (0.0-2.7)
0.2 (0.0-1.7)
p=0.360
Continence (%)
7.69
31.62
20.80
50.41
Median no. pads used/day
2.0 (0.0-3.4)
1.0 (0.0-2.0)
p=0.010
Dosage (mg)
16.72
20.89
9.75
13.59
Mean MS QoL 54 (total)
Baseline (SD)
8 weeks (SD)
Paired T-Test
113.1 (30.9)
116.1 (30.9)
p=0.955
CONCLUSIONS: Solifenacin is effective in the treatment of MS patients with complaints of a neurogenic overactive bladder. Both on complaints of urgency frequency and urge incontinence significant improvements were observed. The MS QoL 54 is not sensitive enough to detect changes in lower urinary tract functioning in MS patients.
Eur Urol Suppl 2006;5(2):298
Propiverine was better tolerated than oxybutynin in the total study population (9.40% versus 17.46% adverse events overall). No serious adverse events occurred. Oxybutynin had to be used in dosages twice as high as recommended to achieve the goals, whereas propiverine was administered in dosages lower than recommended. CONCLUSIONS: Despite statistical superiority of propiverine efficacy results have to be discussed with precaution: urodynamic baseline values of both groups differ, urodynamic curves (e.g. compliance) might have been interpreted different at 14 study centres, and heterogenity of patients must be considered. The significantly more effective treatment response of propiverine compared to oxybutynin in the total population was due to an enhanced response of MMCchildren to propiverine, which might be due to the additional calcium-channel-modulating effects of propiverine. The superior tolerability profile of propiverine compared to oxybutynin was confirmed also in children with NDO.