Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new ditropan research articles will be listed here shortly after becoming available to us.
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Int J Clin Pract. 2008 Sep 22;
Zinner N, Kobashi KC, Ebinger U, Viegas A, Egermark M, Quebe-Fehling E, Koochaki P
Introduction and objective: Patient perception of overactive bladder (OAB) treatment outcomes can be a useful indicator of benefit and may help drive persistence on treatment, which is known to be poor in OAB. It remains unclear whether OAB patients dissatisfied with one antimuscarinic can achieve satisfaction with another and supporting data are limited. This study investigated patient-reported outcomes and clinical parameters during darifenacin treatment in OAB patients who expressed dissatisfaction with prior extended-release (ER) oxybutynin or tolterodine therapy (administered for >/= 1 week within the past year). Methods: This open-label study was conducted in darifenacin-naïve OAB patients. Patients received 7.5 mg darifenacin once daily with the possibility of up-titrating to 15 mg after 2 weeks, for up to 12 weeks. Efficacy parameters included the Patient's Perception of Bladder Condition (PPBC), patient satisfaction with treatment, micturition frequency and number of urgency and urge urinary incontinence (UUI) episodes. Adverse events (AEs) were also recorded. Results: In total, 497 patients were treated (84.1% women). Darifenacin treatment resulted in statistically significant improvements in PPBC scores, micturition frequency, urgency and UUI episodes from baseline at 12 weeks. The improvements were similar for patients previously treated with oxybutynin ER or tolterodine ER. More than 85% of patients expressed satisfaction with darifenacin. As noted in other studies, the most common AEs were dry mouth and constipation, but these infrequently resulted in treatment discontinuation, which was low overall. Conclusions: In this study, PPBC score and OAB symptoms were significantly improved, and satisfaction was high during treatment with darifenacin (7.5/15 mg) in patients who were dissatisfied with the previous antimuscarinic treatment.
Contraindicated medication use among patients in a memory disorders clinic.
Am J Geriatr Pharmacother. 2008 Aug; 6(3): 147-52
Barton C, Sklenicka J, Sayegh P, Yaffe K
BACKGROUND: Inappropriate or contraindicated use of medications in elderly patients is common and associated with poor outcomes. An important risk factor for adverse drug events is the increased sensitivity to drug effects on the central nervous system (CNS). There is a high rate of use of CNS-active drugs in patients with cognitive impairment, despite the fact that these medications may worsen cognition and be a possible "reversible" cause of memory loss. OBJECTIVES: The goals of this study were to establish the prevalence of these contraindicated medications in a population of elderly patients referred to a memory disorders clinic for evaluation and to determine if those individuals receiving contraindicated medications had specific characteristics. This included determining how many patients were concurrently being prescribed a cholinesterase inhibitor. METHODS: The review included new patients consecutively evaluated for cognitive complaints in a memory disorders clinic between June 2003 and August 2004. Each patient underwent a comprehensive evaluation by a multi-disciplinary team during a 3-hour clinic appointment. A thorough history of cognitive deficits and associated symptoms was obtained by the physician, who also performed a comprehensive neurologic examination. All patients underwent neuropsychologic testing with an extensive cognitive battery. In addition, patients' electronic medical records were reviewed to determine a list of prescribed and over-the-counter medications at the time of the initial referral. Contraindicated medications were identified using the updated Beers criteria of medications that should be avoided in older patients with cognitive impairment or that have high CNS adverse effects. RESULTS: A total of 100 patients (91 men, 9 women; mean [SD] age, 75.8 [9.7] years; 73% white) were included in the study. Eighty-six patients were determined at the time of evaluation to have some kind of cognitive impairment. They were mildly impaired, with a mean (SD) Mini-Mental State Examination score of 22.9 (5.1), based on a scale of 0 to 30. Twenty-two patients were taking > or =1 contraindicated medication that could potentially affect their cognition; the most frequently prescribed were benzodiazepines, oxybutynin, amitriptyline, fluoxetine, and diphenhydramine. Twenty-eight of the 100 patients were being treated with a cholinesterase inhibitor at the time of their evaluation; of these, 4 (14%) were also taking > or =1 medication with anticholinergic properties. CONCLUSIONS: Despite research evidence and recommendations to avoid these CNS-active medications because of their adverse effects, they continue to be prescribed in elderly patients with cognitive impairments. Further research is needed to determine strategies that will help reduce their administration in this population.
Mayo Clin Proc. 2008 Sep; 83(9): 1002-10
MacDiarmid SA, Peters KM, Chen A, Armstrong RB, Orman C, Aquilina JW, Nitti VW
OBJECTIVE: To evaluate the efficacy and tolerability of extended-release oxybutynin in combination with the alpha1-blocker tamsulosin in reducing lower urinary tract symptoms in men. PATIENTS AND METHODS: In this multicenter, double-blind trial performed between March 29, 2004, and June 22, 2005, 420 men aged 45 years or older with a total International Prostate Symptom Score (IPSS) of 13 or more and IPSS for storage of 8 or more were randomized to receive tamsulosin (0.4 mg/d) with either extended-release oxybutynin (10 mg/d) or placebo for 12 weeks. Eligibility requirements included a maximum flow rate of 8 mL/s or more with voided volume of 125 mL or more and a postvoid residual volume of 150 mL or less on 2 occasions. Postvoid residual volume and peak flow rates at weeks 4, 8, and 12 were measured. The primary end point was change from baseline in total IPSS after 12 weeks of treatment. Secondary outcomes included change in IPSSs for storage and quality of life. RESULTS: Tamsulosin combined with extended-release oxybutynin resulted in significantly greater improvement in total IPSS compared with tamsulosin and placebo after 8 (P=.03) and 12 (P=.006) weeks of treatment, and improved IPSS for storage and quality of life at all assessment points (P
J Urol. 2008 Oct; 180(4): 1486-93; discussion 1494-5
Bael A, Lax H, de Jong TP, Hoebeke P, Nijman RJ, Sixt R, Verhulst J, Hirche H, van Gool JD,
PURPOSE: The objective of this study was to compare prospectively, in urge syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns, to assess changes in urodynamic patterns after treatment, and to correlate urodynamic patterns and parameters with treatment outcome. MATERIALS AND METHODS: In the European Bladder Dysfunction Study 97 children with clinically diagnosed urge syndrome received standard treatment, to which was randomly added placebo, oxybutynin or bladder training with online feedback. In a separate branch 105 children with clinically diagnosed dysfunctional voiding were randomly allocated to standard treatment or standard treatment plus pelvic floor training with online feedback. In all children urodynamic studies were performed before and immediately after treatment. RESULTS: In urge syndrome detrusor overactivity was present in 33% of cases before and 27% after treatment (of which 65% were de novo). Detrusor overactivity did not correlate with treatment outcome. In dysfunctional voiding increased pelvic floor activity during voiding, which was present in 67% of cases before and 56% after treatment (of which 45% were de novo), did not correlate with treatment outcome. In urge syndrome as well as in dysfunctional voiding neither maximum detrusor pressure during voiding, cystometric bladder capacity, bladder compliance nor free flow patterns correlated with treatment outcome. CONCLUSIONS: Neither detrusor overactivity nor increased pelvic floor activity during voiding correlated with treatment outcome. Standard treatment could be the first choice in urge syndrome as well as in dysfunctional voiding, reserving urodynamic studies for patients in whom this first approach fails.
Int J Clin Pract. 2008 Aug 11;
Kay GG, Ebinger U
Background: Antimuscarinic agents used in the treatment of overactive bladder (OAB) differ in their potential to impair cognitive function. It is hypothesised that low brain concentrations and relatively low selectivity for the M(1) muscarinic receptor may reduce the potential for adverse central nervous system (CNS) effects with darifenacin, compared with other antimuscarinics, particularly oxybutynin. Methods: Cognitive function studies evaluating darifenacin, oxybutynin, tolterodine, solifenacin and/or trospium were identified from publications databases (Medline, Biosis and Embase) and congress abstracts. Preclinical studies and randomised controlled trials in adults were reviewed. Results: Five randomised, double-blind, multiple-dose studies of cognitive function were identified. Oxybutynin was consistently associated with cognitive deficit (four studies), whereas darifenacin did not impair cognition (three studies). These findings were supported by data from sleep/attention and EEG studies. Tolterodine data were limited to one small study with each formulation. For solifenacin and trospium, there were no human studies evaluating memory, the cognitive function most vulnerable to CNS anticholinergics. Conclusions: There is compelling evidence of cognitive impairment with oxybutynin, whereas darifenacin stands out by demonstrating no impairment of memory or other cognitive functions in three randomised, controlled trials. This may be attributed to the differences in physicochemical properties, efflux mechanisms and relative M(1) muscarinic receptor sparing. The risk of CNS impairment is of particular concern for vulnerable populations such as the elderly (a substantial proportion of the OAB population), and CNS-compromised neurogenic bladder patients such as those with multiple sclerosis or Parkinson's disease.
Chem Pharm Bull (Tokyo). 2008 Aug; 56(8): 1073-6
Hanawa T, Tsuchiya C, Endo N, Hanawa K, Suzuki M, Suzuki T, Mohri K, Oguchi T
A formulation study of intravesical oxybutynin (OB) preparations was carried out in order to improve the effectiveness in intravesical instillation therapy for spastic neurogenetic bladder. Sodium hyaluronate (HYA) was introduced to enhance the muco-adhesiveness of the instillation preparation, and the physicochemical properties of the OB formulation were evaluated in comparison with a conventional formulation containing hydroxypropylcellulose (HPC). The viscous properties and in vitro adhesiveness increased with the amount of the polymeric additives, and retention properties of OB in rabbit bladder were comparable after addition of 0.4% HYA and 1.0% HPC. HYA was able to enhance the intravesical retention properties of OB instillation solution to a lesser degree than HPC, it seemed to be a useful additive in the OB instillation due to its safety and mucosal-protective effect.
Urologiia. 2008 May-Jun; 17-8, 20
Artamonov VA, Rybnikov SV
Laparoscopic retropubic urethropexy by Birch was followed by chemotherapy with m-cholinolytics in 30 women with mixed urinary incontinence. 15 patients received trospium chloride in a daily dose 30-45 mg and the other 15--oxibutinin hydrochloride in a daily dose 10-15 mg. A comparative analysis of the treatment results after 36 months of follow-up demonstrated higher safety of trospium chloride which showed the same efficacy with oxibutinin hydrochloride.
Sonographic evaluation of gallbladder contractility in patients with spinal cord injury.
J Clin Ultrasound. 2008 Oct; 36(8): 467-71
Nakayama M, Távora DG, Gama RL, Silva CE
PURPOSE: To determine gallbladder volume with sonography during fasting and in response to a fatty meal in patients with spinal cord injuries (SCIs) and compare the results with those obtained in healthy controls. METHOD: Forty-three patients with SCI and 40 healthy volunteers without clinical evidence of gallbladder disease underwent sonography before and 30 and 60 minutes after the ingestion of a standard fatty meal. The gallbladder fasting volume, resting volume, and gallbladder contractility were calculated, and the results were compared. Correlation between gallbladder contractility and level of lesion, time since injury, use of oxybutynin, and body mass index (BMI) was also assessed. RESULTS: The mean ejection fraction was significantly lower in the patients with SCIs (40%) compared with healthy controls (63%) (p < 0.001). Gallbladder mean residual volume 60 minutes after ingestion of the fatty meal was lower in the control group (p < 0.001). CONCLUSION: Gallbladder contractility is impaired in patients with SCI, which may predispose these patients to gallstone formation. There was no correlation between gallbladder contractility and level of the lesion, time since injury, use of oxybutynin, or BMI.
Intravesical oxybutynin for children with poorly compliant neurogenic bladder: a systematic review.
J Urol. 2008 Sep; 180(3): 1091-7
Guerra LA, Moher D, Sampson M, Barrowman N, Pike J, Leonard M
PURPOSE: Children with neurogenic bladder and poor bladder compliance are usually treated with bladder catheterization and oral anticholinergic medication. They may become nonresponders to the drug or present with severe side effects. We evaluated the effectiveness and tolerability of intravesical oxybutynin in children with poorly compliant neurogenic bladder. MATERIALS AND METHODS: We conducted a search of MEDLINE, EMBASE, CINAHL, SciELO, dissertations/theses in ProQuest, LILACS, the Cochrane Library, protocol registries and the gray literature. Two reviewers independently assessed study quality and extracted data. RESULTS: Eight studies (2 prospective, 6 retrospective) assessed the effectiveness and side effects of intravesical oxybutynin in children with neurogenic bladder. A total of 297 children started treatment, of whom 22% (66 patients) discontinued therapy, with 9% (28) quitting due to systemic side effects. Mean change in bladder compliance (primary outcome) was reported in only 2 studies (+7.4 and +7.5 ml/cm H(2)O). The pooled mean change in pressure at maximum bladder capacity was -16.4 cm H(2)O (95% CI -22.8 to -10.0). Incontinence improved significantly in most studies, with "dry and improved" rates ranging from 61% to 83%. The funnel plot of pressure at maximum bladder capacity suggested no publication bias. CONCLUSIONS: Adjunctive intravesical oxybutynin therapy increased mean maximum bladder capacity and decreased bladder pressure in children with neurogenic bladder. However, identified studies offered a low level of evidence, with most being poorly reported retrospective case series with potential biases. Although the incidence of side effects was lower with the intravesical route, side effects are still possible and should be discussed with patients and families. The evidence available is insufficient to recommend this therapy. Research of more sound study design such as a randomized controlled trial should be conducted to assess the efficacy and side effects of intravesical oxybutynin in children.
Eur Urol. 2008 Oct; 54(4): 740-64
Novara G, Galfano A, Secco S, D'Elia C, Cavalleri S, Ficarra V, Artibani W
CONTEXT: Anticholinergic drugs are commonly used in patients with overactive bladder (OAB) who do not achieve symptom relief and quality of life improvement with conservative management. Several drugs, with different doses, formulations, and routes of administration are currently available, making the choice quite difficult. OBJECTIVE: To evaluate efficacy and safety of different doses, formulations, and route of administration of the available anticholinergic drugs. EVIDENCE ACQUISITION: A systematic review of the literature was performed in August 2007 using Medline, Embase, and Web of Science. Efficacy (micturitions per 24h, volume voided per micturition, urgency urinary incontinence episodes per 24h, incontinence episodes per 24h) and safety (mainly, adverse events and withdrawal rates) end points were evaluated in the randomized control trials (RCTs) assessing the role of anticholinergic drugs in non-neurogenic OAB. Meta-analysis of RCTs was conducted using the Review Manager software 4.2 (Cochrane Collaboration). EVIDENCE SYNTHESIS: Our systematic search identified 50 RCTs and three pooled analyses. Tolterodine immediate release (IR) had a more favorable profile of adverse events than oxybutynin IR. Regarding different dosages of IR formulations, dose escalation might yield some limited improvements in the efficacy but at the cost of significant increase in the rate of adverse events. In the comparisons between IR and extended-release (ER) formulations, the latter showed some advantages, both in terms of efficacy and safety. With regard to the route of administration, use if a transdermal route of administration does not provide significant advantage over an oral one. CONCLUSION: Many of the available RCTs have good methodological quality. ER formulations should be preferred to the IR ones. With regard to IR formulations, dose escalation might yield some improvements in the efficacy with significant increase in the AE. More clinical studies are needed to indicate which of the drugs should be used as first-, second-, or third-line treatment.