tolterodine-tartrate and oxybutynin

This study aimed to estimate the cost-utility of effective interventions for enuresis treatment in children and adolescents and to calculate the incremental cost-utility ratio from the perspective of the Brazilian Unified Health System in a 1-year time horizon.. The economic analysis is in 7 stages: (1) survey of evidence of treatments for enuresis, (2) performing the network meta-analysis, (3) estimation of the probability of cure, (4) cost-utility analysis, (5) model sensitivity analysis, (6) analysis of acceptability of interventions by acceptability curve, and (7) monitoring the technological horizon.. The association between desmopressin and oxybutynin is the therapeutic strategy with the highest probability of success in the treatment of enuresis in children and adolescents compared with placebo (relative risk [RR] 2.88; 95% confidence interval [CI] 1.65-5.04), followed by the combination therapy between desmopressin and tolterodine (RR 2.13; 95% CI 1.13-4.02), alarm (RR 1.59; 95% CI 1.14-2.23), and neurostimulation (RR 1.43; 95% CI 1.04-1.96). Combination therapy between desmopressin and tolterodine was the only 1 considered not to be cost-effective. Neurostimulation, alarm therapy, and therapy had the respective incremental cost-utility ratio values: R$5931.68, R$7982.92, and R$29 050.56/quality-adjusted life-years.. Among the therapies that are on the borderline of efficiency, the combined therapy between desmopressin and oxybutynin presents the greatest incremental benefit at an incremental cost that is still feasible, given that it does not exceed the reference value of the cost-effectiveness threshold established in Brazil.

Topics: Adolescent; Brazil; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Tolterodine Tartrate

Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.

Topics: Benzhydryl Compounds; Benzofurans; Cholinergic Antagonists; Cognition; Cognitive Dysfunction; Dementia; Humans; Mandelic Acids; Prodromal Symptoms; Pyrrolidines; Risk Assessment; Risk Factors; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

overactive bladder (OAB) affects 17-41% older adults in community dwelled setting. For several years, antimuscarinics have been validated as the first-line medical treatment for OAB. Despite abundant data obtained from clinical trials provisions the use of antimuscarinics, investigation about the effect of this drug on cognitive function in elderly remains scarce. The objective of this study is to investigate the effect of antimuscarinics therapy on cognitive functions in OAB geriatric patients.. this study design is a systematic review and meta-analysis. Studies were collected using several search engines; those were PubMed, Science Direct, Cochrane, and EBSCOhost using predetermined MeSH keywords with Boolean operators. Selection of studies was done by three reviewers. Studies which fulfilled the inclusion and exclusion criteria underwent full-text review. For every selected full text, we extracted the following data if available: patients demographics, types of antimuscarinics used, placebo, dose, follow-up period, and Mini-Mental State Examination (MMSE) total score.. a total of 8 studies from an initial 146 publications were selected. There were 8 antimuscarinic agents evaluated in the studies, including Oxybutynin, Darifenacin, Tolterodine, Trospium, Imidafenacin, Propiverine hydrochloride, Fesoterodine, and Solifenacin. Oxybutynin was shown to have largest effect towards the decline of MMSE score [Mean difference: -2.90; 95% CI: -4.07, -1.73]. Darifenacin and Tolterodine were also shown to be significant in the decline of total MMSE score, although still inferior to Oxybutynin.. the use of most antimuscarinics medication has little to no effect towards the cognitive function in the management of overactive bladder in elderly patients. However, Oxybutynin, Darifenacin, and Tolterodine was shown to have significant decrease in cognitive functions, as shown in the decline of total MMSE score.

Topics: Aged; Benzofurans; Cognition Disorders; Humans; Mandelic Acids; Mental Status and Dementia Tests; Muscarinic Antagonists; Pyrrolidines; Tolterodine Tartrate; Urinary Bladder, Overactive

To carry out a network meta-analysis of randomised controlled trials (RCTs) of anticholinergic drug treatment for people with overactive bladders.. Comprehensive searches for relevant RCTs were carried out starting with RCTs included in previous systematic reviews with the last search in February 2017. Searches included terms for the anticholinergic drugs tolterodine, oxybutynin, trospium, propiverine, solifenacin, darifenacin, imidafenacin, and fesoterodine. Data was extracted from the systematic reviews or reports of studies for cure or improvement, voids per 24 hr, leakage episodes per 24 hr and dry mouth. Data was analysed using frequentist network meta-analysis.. 128 studies were found. There was no clearly best treatment for cure or improvement. The differences between treatments for voids and leakages were small and unlikely to be of clinical importance. Transdermally delivered oxybutynin was clearly the best treatment for dry mouth but was still worse than placebo.. All the anticholinergic drugs were better than placebo but apart from dry mouth were similar in effect. Transdermal oxybutynin caused less dry mouth than the other treatments, so may be worth considering as the first treatment.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Humans; Imidazoles; Mandelic Acids; Network Meta-Analysis; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB).. Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics.. The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation.. This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

Topics: Benzhydryl Compounds; Benzilates; Humans; Mandelic Acids; Muscarinic Antagonists; Network Meta-Analysis; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments.. To compare the effects of different anticholinergic drugs for overactive bladder symptoms.. We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 March 2011) and reference lists of relevant articles.. Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug.. Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook.. Eighty six trials, 70 parallel and 16 cross-over designs were included (31,249 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analyses. Twenty nine collected quality of life data (the primary outcome measure) using validated measures, but only fifteen reported useable data.Tolterodine versus oxybutynin: There were no statistically significant differences for quality of life, patient reported cure or improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events with tolterodine (Risk Ratio (RR) 0.52, 95% confidence interval (CI) 0.40 to 0.66, data from eight trials), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71, data from ten trials).Solifenacin versus tolterodine: There were statistically significant differences for quality of life (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01, data from three trials), patient reported cure/improvement (RR 1.25, 95% CI 1.13 to 1.39, data from two trials), leakage episodes in 24 hours (weighted mean difference (WMD) -0.30, 95% CI -0.53 to -0.08, data from four studies) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13, data from four trials), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth, but after sensitivity analysis the dry mouth (RR 0.69, 95% CI 0.51 to 0.94) was statistically significantly lower with solifenacin when compared to Immediate Release (IR) tolterodine.Fesoterodine versus extended release tolterodine: Three trials contributed to the meta analyses. There were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14), patient reported cure/improvement (RR 1.11, 95% CI 1.06 to 1.16), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09), frequency (WMD -0.27, 95% CI -0.47 to -0.06) and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16) in 24 hours, all favouring fesoterodine, but those taking fesoterodine had higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05) at 12 weeks.Different doses of tolterodine: The standard recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effects of 1 mg, 2 mg and 4 mg doses were similar for leakage. Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective, with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth.Between solifenacin and immediate release tolterodine, solifenacin might be preferred for better efficacy and less risk of dry mouth. Solifenacin 5 mg once daily is the usual starting dose, this could be increased to 10 mg once daily for better efficacy but with increased risk of dry mouth.Between fesoterodine and extended release tolterodine, fesoterodine might be preferred for superior efficacy but has higher risk of withdrawal due to adverse events and higher risk of dry mouth.There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Topics: Adult; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Phenylpropanolamine; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

Urinary incontinence (UI) in women adversely affects quality of life.. To conduct a systematic literature review of drugs for urgency UI in women.. MEDLINE, the Cochrane Central Register of Controlled Trials, SCIRUS, and Google Scholar were searched for articles published from 1966 to November 2011.. Randomized, controlled trials (RCTs) reported in English.. Rates of outcomes and risk of bias were extracted by using a standardized form to pool absolute risk differences and calculate the number of attributable events per 1000 patients treated, with 95% CIs.. 94 RCTs were eligible. Pooled analyses showed that among drugs for urgency UI, per 1000 treated women, continence was restored in 130 with fesoterodine (CI, 58 to 202), 85 with tolterodine (CI, 40 to 129), 114 with oxybutynin (CI, 64 to 163), 107 with solifenacin (CI, 58 to 156), and 114 with trospium (CI, 83 to 144). Rates of treatment discontinuation due to adverse effects were 31 per 1000 treated with fesoterodine (CI, 10 to 56), 63 with oxybutynin (CI, 12 to 127), 18 with trospium (CI, 4 to 33), and 13 with solifenacin (CI, 1 to 26). The studies' inconsistent definitions of reduction in UI and quality of life hampered synthesis of evidence.. Evidence for quality-of-life improvements and comparative effectiveness with drugs was limited, and evidence for the effects of race, baseline severity of UI, and comorbid conditions on treatment success was insufficient.. Overall, drugs for urgency UI showed similar small benefit. Therapeutic choices should consider the harms profile. Evidence for long-term adherence and safety of treatments is lacking.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Comparative Effectiveness Research; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quality of Life; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs).. The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse events, pharmacokinetics, tolerability" in combination with "darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.". Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Chronic Disease; Cresols; Drug Combinations; Female; Humans; Imidazoles; Mandelic Acids; Muscarinic Antagonists; Nocturia; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

The medical treatment of children with non-neurogenic overactive bladder syndrome (OAB) is still limited to a small number of drugs approved for use in childhood according to the national regulations of each country.. Over the last few years, there were several studies on the use of antimuscarinics other than oxybutynin in children, as well as some on the use of extended release oxybutynin and tolterodine and transdermal oxybutynin. It was shown that the combination of two different anticholinergics might be a well tolerated and successful option in children with OAB refractory to monotherapy, as well as administration of a receptor-selective antimuscarinic such as solifenacin. European studies showed promising outcomes using propiverine, and good results were achieved in the majority of patients by injection of botulinum toxin into the detrusor.. After exhaustion of conservative standard treatment (i.e. urotherapy), medical treatment should be considered for children with non-neurogenic OAB. Oxybutynin or off-label use of an agent that has been shown to be well tolerated and effective should be given preference over the use of medication that has not yet been evaluated in children. Randomized controlled studies on newer and receptor-selective anticholinergics, combination therapy, and botulinum toxin in children are needed.

Topics: Benzhydryl Compounds; Benzilates; Botulinum Toxins; Child; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Quinuclidines; Receptors, Muscarinic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urination

A randomized, double-blind, placebo- and active comparator-controlled study was conducted in 69 centers to compare detrusitol and oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). Detrusitol had similar efficacy but was better tolerated than oxybutynin in Japanese and Korean patients with OAB. The study result was acknowledged as pivotal data in the clinical data package when NDA was filed and successfully approved both in Japan and Korea. Some differences were found in the efficacy and safety of the drug between the Japanese and Korean data, though. We therefore investigated the differences through stratified analysis; however exact causes could not be identified. This study is positioned as a first multinational clinical trial conducted in East Asia. From the aspects of utilization of interoperable data obtained from such multinational clinical trials for NDA filing and earliest possible registration of drugs in the participating countries, we believe it is important to accumulate more experiences in conducting multinational clinical trials. At this time, it is our prime task to minimize the "drug lag" in Japan; I think improving the speed of clinical trials is one of the factors to solve the issue. Global clinical trials involving Western and Asian countries make it possible to use the study data effectively and commonly in many countries. Moreover, from the viewpoint of revitalization of clinical trials, conducting global clinical trials is critically important; so we intend to continue accumulation of our experiences in global clinical trials.

Topics: Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; International Cooperation; Japan; Korea; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Overactive

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.. To evaluate efficacy and safety of different doses, formulations, and route of administration of the available anticholinergic drugs.. 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).. 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.. 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.

Topics: Benzhydryl Compounds; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Overactive

Urinary incontinence in women is a common problem that adversely affects quality of life.. To synthesize evidence of management of urinary incontinence in women.. MEDLINE, CINAHL, and the Cochrane Library.. 96 randomized, controlled trials (RCTs) and 3 systematic reviews published in English from 1990 through May 2007.. Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference.. Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Different injectable bulking agents and medical devices were associated with similar continence and improvement rates. Electrical stimulation failed to resolve urinary incontinence. Oral hormone administration increased rates of urinary incontinence compared with placebo in most RCTs (1243 women). Transdermal or vaginal estrogen resulted in inconsistent improvement of urinary incontinence. Adrenergic drugs did not resolve or improve urinary incontinence. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose-response association.. Inconsistent measurements of outcomes limited the findings. Predictors of better effect have not been identified in RCTs.. Moderate levels of evidence suggest that pelvic floor muscle training and bladder training resolved urinary incontinence in women. Anticholinergic drugs resolved urinary incontinence, with similar effects from oxybutynin or tolterodine. Duloxetine improved but did not resolve urinary incontinence. The effects of electrostimulation, medical devices, injectable bulking agents, and local estrogen therapy were inconsistent.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Collagen; Cresols; Duloxetine Hydrochloride; Electric Stimulation Therapy; Estrogen Replacement Therapy; Exercise Therapy; Female; Humans; Magnetics; Mandelic Acids; Pelvic Floor; Pessaries; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiophenes; Tolterodine Tartrate; Urinary Incontinence

Millions of men suffer from overactive bladder and lower urinary tract symptoms. The adverse effects on quality of life and costs associated with the condition have been well described. In men, the pathophysiology of lower urinary tract symptoms may be from a number of causes including bladder outlet obstruction, detrusor overactivity, or both. Increasing data and clinical experience support the efficacy and safety of anticholinergics in men; the rate of urinary retention has been equal to that of placebo in short-term studies. Urodynamics play a vital role in defining the bladder and/or outlet dysfunction and help direct one's therapy.

Topics: Adult; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Cystoscopy; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Multicenter Studies as Topic; Phenylpropanolamine; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive; Urodynamics

To analyze the relationship between mean volume voided per micturition and number of daytime micturitions.. We reviewed data from randomized clinical trials on the medical treatment of overactive bladder published in the international literature between 1997 and 2004. Fourteen studies including data on these two parameters were identified.. Six studies compared tolterodine with placebo, two tolterodine and oxybutynin with placebo, two tolterodine with oxybutynin, two solifenacin and tolterodine with placebo, one oxybutynin CR with oxybutynin IR, and one different doses of solifenacin. The correlation between the percent change in the mean voided volume and in the number of daytime micturitions was assessed using the Spearman rank correlation coefficient (r), with r=-0.67 for all the studies. For groups of patients treated with each drug, we found r=-0.09 for oxybutynin, r=-0.59 for tolterodine, r=-0.85 for solifenacin, and r=-0.34 for placebo.. The results of this analysis suggest that in the evaluation of the efficacy of a drug for overactive bladder, the mean volume voided per micturition may be a useful measure of efficacy.

Topics: Benzhydryl Compounds; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urination

Overactive bladder (OAB) is highly prevalent in the older population and decreases quality of life. Current therapy consists primarily of anticholinergic drugs. Because older individuals typically take multiple medications, clinicians must pay special attention to potential drug-drug interactions that may cause adverse events or alter drug efficacy. The most clinically important drug-drug interactions occur during cytochrome P450 (CYP450) isoenzyme metabolism, resulting in altered metabolism of one or more of the coadministered agents. Of the drugs indicated for OAB, tolterodine, darifenacin, solifenacin, and oxybutynin are extensively metabolized by CYP450, but trospium is not. Trospium is eliminated as unchanged drug, suggesting that it has lower potential for drug-drug interactions and may, therefore, represent a safer treatment option for OAB, particularly in the context of polypharmacy, a significant concern in older adults.

Topics: Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Overactive bladder (OAB) is a prevalent condition in both men and women that imposes significant burdens on the patient and his or her quality of life. Nevertheless, only a small percentage of patients with OAB receive diagnosis and treatment. The identification of OAB is well within the scope of the primary care provider, as it is symptom-based and does not generally require specialized testing. The treatment of OAB relies on behavioral modification and/or pharmacologic options, primarily antimuscarinic therapy. Better identification of OAB symptoms in the primary care setting should reduce the number of patients suffering from untreated OAB.

Topics: Benzhydryl Compounds; Cost of Illness; Cresols; Female; Humans; Male; Mandelic Acids; Mass Screening; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Quality of Life; Tolterodine Tartrate; Urinary Bladder, Overactive

Around 1.5% of adults in Europe and the USA have urge urinary incontinence (involuntary leakage immediately preceded or accompanied by urgency). This is usually due to overactive bladder syndrome (defined as urgency, with or without urge incontinence, and usually with frequency and nocturia), which occurs in around 12% of adults, and is similarly prevalent in men and women. We last reviewed this condition in 2001. Since then, two new antimuscarinic drugs, darifenacin (Emselex) and solifenacin (Vesicare) have been licensed in the UK for urge incontinence and/or increased urinary frequency and urgency (as may occur in patients with overactive bladder syndrome), as have transdermal oxybutynin (Kentera) and modified-release formulations of tolterodine (Detrusitol XL) and propiverine (Detrunorm XL). Here we review the place of these newer drugs and formulations.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

To evaluate the effects of individual and condition characteristics on satisfaction with extended release tolterodine or oxybutynin in overactive bladder (OAB).. Data were from the 2005 National Health and Wellness Survey, an annual, nationally representative, self-administered, internet-based survey of 40,000+ US adults (age 18+). Inclusion criteria for analysis were diagnosed OAB and using extended release tolterodine or oxybutynin but no other prescription medications for OAB. Satisfaction with extended release tolterodine or oxybutynin was rated on a five-point scale from 1 = not at all satisfied to 5 = extremely satisfied. Linear regression was used to evaluate independent effects demographics, patient perception of OAB, duration of use, requesting of medication, type of prescribing physician, medication compliance, and mental and physical health-related quality of life (Medical Outcomes Study, Eight-item Short-Form Health Survey; SF-8) on treatment satisfaction.. There were 345 patients who met the inclusion criteria. Apparent predictors of medication satisfaction, in order of magnitude of effect, were: feelings that OAB is just an inconvenience (standardized beta = -0.28; p < 0.001); less impact of OAB on daily life (standardized beta = 0.24; p < 0.001); longer duration of use (standardized beta = 0.10; p = 0.052); overwhelming urges to urinate (standardized beta = 0.10; p = 0.061); younger age (standardized beta = -0.10; p = 0.054); and more frequent medication use (standardized beta = 0.09; p = 0.096).. Data were cross-sectional and self-reported by patients via the internet.. Patient treatment satisfaction is affected by perceptions of OAB symptoms and impact, as well as consistent, long-term use of prescription treatments. Clinicians should reinforce to patients the importance of long-term compliance for successful treatment.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Patient Compliance; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Bladder, Overactive

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.

Topics: Benzhydryl Compounds; Benzofurans; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder (OAB) affects millions of individuals and may severely impair the quality of life of those affected. The contribution of human behavior to manifestations of this symptom complex remains poorly understood. Continued evolution of our understanding of the pathophysiology of OAB has identified contributory mechanisms, which in turn may open new therapeutic avenues. Recent improvements in drug delivery systems represent advances in the management of OAB. However, more complete symptom control with greater tolerability is desirable; this awaits the development of agents specific for newly emerging and as yet unidentified pathophysiologic pathways. Importantly, as understanding of outcomes assessment in OAB matures, refined assessments of disease severity, response to intervention, and patient preference should be possible.

Topics: Animals; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle Contraction; Parasympatholytics; Patient Compliance; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Overactive bladder (OAB) is a chronic syndrome with debilitating symptoms that negatively affect health-related quality of life. Although anticholinergic agents have been first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Anticholinergic agents prevent involuntary contractions of the bladder detrusor muscle by preventing acetylcholine from binding to the M2 and M3 muscarinic receptor subtypes. Anticholinergics are not tissue specific, and their use for treatment of OAB has been associated with side effects such as dry mouth, constipation, and blurred vision. Recent studies with extended-release formulations and newly developed receptor subtype-specific anticholinergic agents demonstrate that side effects are typically mild to moderate and generally tolerable, seldom leading to patient withdrawal. By incorporating patient-initiated dose adjustment into the protocol, the primary care physician can effectively manage adverse events associated with OAB without compromising efficacy. Recent dose-adjustment data with extended-release oxybutynin suggest that, given some control in the process, patients are willing to tolerate certain side effects in exchange for symptom relief.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Overactive bladder is a common and distressing problem. Standard therapy is directed towards modifying the detrusor motor sensitivity and response via anticholinergic medication. Currently available medications are reviewed and alternative targets for treatment are presented.

Topics: Acetylcholine; Amines; Animals; Anticonvulsants; Benzhydryl Compounds; Cresols; Cyclohexanecarboxylic Acids; Drug Evaluation, Preclinical; Gabapentin; gamma-Aminobutyric Acid; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Product Surveillance, Postmarketing; Quinuclidines; Randomized Controlled Trials as Topic; Receptor, Muscarinic M3; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Topics: Administration, Cutaneous; Administration, Intravesical; Administration, Oral; Algorithms; Animals; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Models, Animal; Phenylpropanolamine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence

To determine if there is a significant difference in outcomes of clinical trials funded by industry or not of antimuscarinic medications used to treat overactive bladder (OAB) symptoms and detrusor overactivity (DOA).. A Medline search was conducted from January 1966 to June 2003 to identify human clinical trials of oxybutynin and tolterodine published in English. Randomized controlled trials on subjects aged > or = 16 years who were being treated with oxybutynin or tolterodine for OAB symptoms or DOA; 24 studies were identified. The endpoints assessed were OAB symptoms or changes in uninhibited detrusor contractions on cystometrography. The outcome variables were dichotomized as 'improvement' or 'no improvement'. Odds ratios and 95% confidence intervals were calculated for each study based on data derived or extracted from tables and figures.. Meta-analysis showed no significant difference in the outcomes trails funded by industry or not. Trials were then reviewed to determine their adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized trials.. Clinical trials are important for clinicians when selecting medical therapies. In this analysis we found no difference in outcomes when comparing studies funded by industry or not for tolterodine and oxybutynin. The quality of all trials would be improved by close adherence to the CONSORT guidelines for randomized clinical trials.

Topics: Benzhydryl Compounds; Cresols; Drug Industry; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Research Support as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Overactive bladder (OAB) is a condition defined by its symptoms--urinary urgency with or without urgency urinary incontinence and often with frequency and nocturia. As such, determining the efficacy of OAB treatments using objective measures, such as urodynamic testing, can be difficult. A better means of gauging treatment efficacy for symptom-based conditions is through the use of patient-reported outcomes (PROs). With PROs, clinicians can gain insight into how a treatment affects a patient's symptoms and whether improvement in symptoms has a positive effect from the patient's perspective. PROs are increasingly being included as end points in clinical trials, including those of antimuscarinic drugs for OAB. Consequently, clinicians should become familiar with the most commonly used instruments. We provide an overview of instruments used to assess symptoms, health-related quality of life, and treatment satisfaction in patients with OAB and discuss how PROs can be incorporated into clinical trial protocols.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Health Status; Humans; Mandelic Acids; Muscarinic Antagonists; Patient Compliance; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence, Stress

Antagonists of muscarinic acetylcholine receptors, such as darifenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium, are the mainstay of the treatment of the overactive bladder syndrome. Fesoterodine is a newer drug awaiting regulatory approval. We briefly review the pharmacological activity of their metabolites and discuss how active metabolites may contribute to their efficacy and tolerability in vivo. Except for trospium, and perhaps solifenacin, all of the above drugs form active metabolites, and their presence and activity need to be taken into consideration when elucidating relationships between pharmacokinetics and pharmacodynamics of these drugs. Moreover, the ratios between parent compounds and metabolites may differ depending on genotype of the metabolizing enzymes, concomitant medication, and/or drug formulation. Differential generation of active metabolites of darifenacin or tolterodine are unlikely to influence the overall clinical profile of these drugs in a major way because the active metabolites exhibit a similar pharmacological profile as the parent compound. In contrast, metabolites of oxybutynin and propiverine may behave quantitatively or even qualitatively differently from their parent compounds and this may have an impact on the overall clinical profile of these drugs. We conclude that more comprehensive studies of drug metabolites are required for an improved understanding of their clinical effects.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

Daytime wetting is a common problem with various causes that can usually be identified through a careful history, thorough physical examination, and urinalysis. Conservative approaches to therapy have a successful outcome in most children. Invasive diagnostic imaging studies and pharmacologic or surgical intervention are necessary only for carefully selected children.

Topics: Arousal; Benzhydryl Compounds; Child; Child, Preschool; Constipation; Cresols; Diurnal Enuresis; Humans; Laughter; Mandelic Acids; Muscarinic Antagonists; Pelvic Floor; Phenylpropanolamine; Toilet Training; Tolterodine Tartrate; Ultrasonography; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Incontinence, Urge; Urodynamics; Vesico-Ureteral Reflux

Overactive bladder is a dreadful syndrome that affects a considerable number of patients. Antimuscarinics are the mainstay of pharmacotherapy for this condition. Transdermal (TD) oxybutynin (OXY) bypasses the first-pass metabolism and reduces the formation of N-desethyloxybutynin, a compound believed to be associated with anticholinergic side effects. The 3.9 mg matrix TD system is applied twice weekly and transports OXY directly into the systemic circulation. The patch can be applied to abdomen, buttock, and hip, and provides continuous OXY delivery that minimizes peak and trough fluctuations in plasma levels. In clinical trials, TD and oral OXY produced a significant reduction in incontinence episodes, with no difference between oral and TD treatments. In addition, TDOXY was similar to tolterodine, and it produced a significant improvement in the number of urinary incontinence episodes, complete continence, and urodynamic and quality of life parameters compared with placebo. The incidence of anticholinergic adverse events with TDOXY was similar to placebo. Most common adverse events were mild-moderate skin reactions. Treatment satisfaction survey suggested patients' preference to use the TD system in the future. Counseling on healthy skin care and appropriate product use can enhance patients' knowledge about TDOXY for overactive bladder treatment.

Topics: Administration, Topical; Benzhydryl Compounds; Cresols; Humans; Mandelic Acids; Parasympatholytics; Patient Satisfaction; Phenylpropanolamine; Technology, Pharmaceutical; Tolterodine Tartrate; Urinary Bladder, Overactive

Primary care physicians must initiate a discussion of overactive bladder and urinary incontinence with their patients who are at risk. A stepwise approach to evaluation and diagnosis and the use of systematic evaluation and treatment algorithms suitable to the primary care setting will improve identification and effective management of the incontinent patient.

Topics: Algorithms; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Imipramine; Mandelic Acids; Phenylpropanolamine; Primary Health Care; Tolterodine Tartrate; Urinary Incontinence; Urinary Incontinence, Stress

Urinary incontinence is caused by an overactive bladder, leading to symptoms of urgency, frequency, and incontinence. Urge incontinence occurs predominantly in women as they age.. This article reviews the current primary literature concerning the efficacy and tolerability of the anticholinergic agent trospium chloride (TCl) in the treatment of overactive bladder with symptoms of urge incontinence, urgency, and frequency. The pharmacokinetics of TCl are also reviewed.. Pertinent articles in English were identified through a search of MEDLINE (1966-present), EMBASE Drugs & Pharmacology (1980-third quarter 2004), Current Contents/Clinical Medicine (week 42, 2003-week 41, 2004), Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, trospium, randomized controlled clinical trial, oxybutynin, tolterodine, scopolamine, imipramine, desipramine, and propantheline.. TCl, a quaternary amine, exhibits high solubility in water but low oral bioavailability (9.6%) and poor central nervous system penetration. Approximately 80% of the absorbed fraction is renally eliminated as unchanged drug via active tubular secretion, with approximately 15% hepatically metabolized into a spiroalcohol and hydrolysis/oxidation products. In 3 placebo-controlled studies, patients who received TCl had an increase in maximum bladder filling capacity and bladder compliance, with a reduction in maximum cystometric capacity (P < 0.005); however, only 1 of these studies showed an increase in bladder compliance, with reductions in maximum detrusor pressure (P < 0.001), number of voids/d (P < or = 0.001), and incontinence episodes/d (P < or = 0.001). In another placebo-controlled study, TCl reduced the number of voids/d and incontinence episodes/d (both, P < or = 0.001). In 2 double-blind studies, TCl and oxybutynin were similarly effective in significantly increasing maximum cystometric capacity and bladder compliance, and in significantly reducing maximum detrusor pressure compared with baseline (all, P < 0.001); there were no significant differences between the 2 treatments at end point. In a third double-blind study comparing TCl and tolterodine with placebo, only TCl significantly reduced the frequency of micturitions/d (P = 0.01). Commonly reported adverse effects in patients receiving TCl included dry mouth, constipation, and headache.. In the 7 studies reviewed, TCl was effective and well tolerated in patients with urge incontinence caused by idiopathic detrusor muscle overactivity or neurogenic detrusor overactivity resulting from spinal cord injury. However, this agent was associated with anticholinergic adverse effects similar to those of other anticholinergic agents; careful monitoring of tolerability is required.

Topics: Aging; Area Under Curve; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Female; Humans; Liver Failure; Male; Mandelic Acids; Metabolic Clearance Rate; Nortropanes; Phenylpropanolamine; Randomized Controlled Trials as Topic; Renal Insufficiency; Tolterodine Tartrate; Urinary Incontinence

Topics: Aged; Behavior Therapy; Benzhydryl Compounds; Cresols; Exercise Therapy; Female; Humans; Male; Mandelic Acids; Mass Screening; Medical History Taking; Middle Aged; Muscarinic Antagonists; Nurse Practitioners; Nurse's Role; Nursing Assessment; Pelvic Floor; Phenylpropanolamine; Physical Examination; Prevalence; Risk Factors; Tolterodine Tartrate; United States; Urinalysis; Urinary Incontinence; Urodynamics

Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments.. To compare the effects of different anticholinergic drugs for overactive bladder symptoms.. We searched the Cochrane Incontinence Group specialised trials register (searched 17 January 2002) and reference lists of relevant articles. A search for full publications of abstracts identified in January 2002 was completed in July 2003.. Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug.. Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook.. Forty nine trials, 39 parallel and 10 cross-over designs were included (11,332 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analysis.Four trials collected quality of life data (the primary outcome measure) using validated measures; none reported useable data. Oxybutynin versus tolterodine: There were no statistically significant differences for patient perceive improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events (RR 0.57, 95% CI 0.43 to 0.75), and less risk of dry mouth (RR 0.60, 95% CI 0.54 to 0.66), with tolterodine. Different doses tolterodine: The usual recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effect of 1 mg, 2 mg and 4 mg doses was similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses.Extended versus immediate release preparations of oxybutynin and/or tolterodine: There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth. One extended release preparation versus another: There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the trandermal patch site.. Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth. There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Topics: Adult; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence

Overactive bladder is a common condition, with recent findings estimating the prevalence in adults at about 15%. Symptoms, including urinary urgency, high voiding frequency and urge incontinence, have been shown to decrease patients' quality of life. Given its high prevalence, the economic burden of overactive bladder is also substantial, with a recent estimate placing the annual cost in the US at 9.1 billion US dollars (year 2000 values). The objective of this review is to provide a critical appraisal of published economic evaluations of pharmacological and non-pharmacological treatments for overactive bladder. Published economic evaluations of treatments for overactive bladder have focused entirely on pharmacological treatments -- mainly on the two most commonly used drugs, oxybutynin and tolterodine, each of which is available in immediate- and extended-release formulations. Ten economic evaluations (more than half are cost-effectiveness studies) have been published. Modelling with decision trees or Markov models has been the predominant method. Evaluations comparing drug therapy with no treatment have concluded that drug therapy is cost effective. Analyses comparing the formulations of oxybutynin and tolterodine have produced highly inconsistent results, largely due to the sources of data employed for effectiveness and treatment discontinuation rates. There are no evaluations of drugs relative to non-pharmacological treatment, and there are other significant gaps in the economic evaluations of treatment to date. These include gaps resulting from a lack of reliable data on the performance of these drugs in real-world settings, particularly data on long-term persistence with treatment. A more definitive pharmacoeconomic comparison of oxybutynin and tolterodine formulations, incorporating all available clinical data, and other treatment options would help direct treatment.

Topics: Benzhydryl Compounds; Cost of Illness; Cresols; Female; Humans; Male; Mandelic Acids; Markov Chains; Middle Aged; Models, Economic; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Behavior Therapy; Benzhydryl Compounds; Biofeedback, Psychology; Cresols; Diagnosis, Differential; Electric Stimulation Therapy; Exercise Therapy; Humans; Incidence; Mandelic Acids; Medical History Taking; Muscarinic Antagonists; Nurse Practitioners; Nurse's Role; Nursing Assessment; Pelvic Floor; Phenylpropanolamine; Physical Examination; Prevalence; Primary Health Care; Referral and Consultation; Toilet Training; Tolterodine Tartrate; United States; Urination Disorders; Urodynamics

Trospium chloride is an orally active, quaternary ammonium compound with antimuscarinic activity. It binds specifically and with high affinity to muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic receptors. It is hydrophilic and does not cross the normal blood-brain barrier in significant amounts and, therefore, has minimal central anticholinergic activity. Peak plasma trospium chloride concentrations are attained approximately 5-6 hours after oral administration, which should occur before meals as concurrent food ingestion significantly reduces trospium bioavailability. Trospium chloride undergoes negligible metabolism by the hepatic cytochrome P450 system; few metabolic drug interactions are known. While trospium chloride dosage adjustments based on age or sex appear unwarranted, such adjustments may be needed in patients with severe renal impairment. Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the efficacy of trospium chloride in terms of improved urodynamic parameters; small-scale, noncomparative studies have documented significant trospium chloride-induced improvements in patients with reflex neurogenic bladder, postoperative bladder irritation and radiation-induced cystitis; and observational studies including >10,000 patients have also revealed favourable findings for trospium chloride, including a marked decrease in incontinence episodes and substantial improvement in health-related quality of life. Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin. The most frequent adverse events, occurring in >1% of trospium chloride-treated patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea. Available for many years in several countries outside North America, trospium chloride is likely to develop an important role in the management of overactive bladder following its approval in the US on 28 May 2004.

Topics: Benzhydryl Compounds; Benzilates; Biological Availability; Cresols; Female; Half-Life; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Randomized Controlled Trials as Topic; Receptors, Muscarinic; Tissue Distribution; Tolterodine Tartrate; Urinary Incontinence

Drug therapy for overactive bladder (OAB) most commonly includes antimuscarinic agents, which work by relaxing bladder smooth muscle through inhibition of acetylcholine receptors in the bladder. The major adverse effects with existing antimuscarinic agents are anticholinergic in nature (e.g., dry mouth, constipation, blurred vision). Oxybutynin and tolterodine have been used for several years for treatment of OAB; both are available in immediate- and extended-release formulations. Fewer or less severe adverse effects are reported with the extended- versus the immediate-release formulations, with little or no difference in efficacy. Oxybutynin is also available as a transdermal patch. Trospium, which was recently approved for use in the United States, has efficacy and an incidence of dry mouth similar to existing agents but does not cross the blood-brain barrier. It requires twice-daily dosing. Two new antimuscarinic agents--darifenacin and solifenacin--are in development. Both show significantly better efficacy compared with placebo for key symptoms of OAB, including urgency. The incidence of dry mouth at the lowest effective dose is 19% for darifenacin and 8% and 14% for solifenacin (2 studies).

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Constipation; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Vision Disorders; Xerostomia

Limitations exist with regard to the array of available agents for the pharmacologic therapy of overactive bladder, including issues of efficacy and tolerability. It is clear that the ideal agent for this condition has not been identified. However, several new pharmacologic treatments, including some with novel approaches to drug delivery, have emerged in clinical development over the past few years. These agents include a variety of anticholinergics and others. In initial studies, some of the agents appear to compare favorably with existing therapies. Whether these promising results will hold up when subjected to large-scale, well-controlled clinical trials is unclear.

Topics: Administration, Cutaneous; Administration, Intravesical; Administration, Oral; Adrenergic beta-3 Receptor Antagonists; Benzhydryl Compounds; Benzilates; Benzofurans; Botulinum Toxins; Cresols; Dosage Forms; Dose-Response Relationship, Drug; Drug Compounding; Drug Evaluation; Duloxetine Hydrochloride; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Thiophenes; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urination Disorders

Overactive bladder (OAB) affects millions of people in the United States and significantly impacts their quality of life. New antimuscarinic anticholinergic medications have improved the treatment of OAB, offering patients efficacy equal to that of immediate-release oxybutynin with fewer side effects and an improved dosing schedule. The commonly reported range of reduction of urge incontinence episodes is between 46% and 92%. Although patients are improving, continence rates are lower and many responders continue to leak significantly. The literature supports that the efficacy of anticholinergics is enhanced by dose escalation, but using higher dosages has not become routine in clinical practice. Although dose escalation can be implemented with all of the anticholinergics, it is done most easily and approved by the US Food and Drug Administration with extended-release oxybutynin. This paper critically evaluates the pros and cons of dose escalation in the hope to improve efficacy in patients with OAB.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Patient Compliance; Patient Satisfaction; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urination Disorders

Recent pharmacologic treatment for detrusor overactivity has resulted in more favorable side effect profiles, not only because of the use of different drug delivery systems for older drugs but perhaps also due to the improved bladder selectivity of newer antimuscarinic agents. These developments translate into higher patient compliance and better long-term results with the newer agents over generic immediate-release oxybutynin for the treatment of the overactive bladder.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urination Disorders

Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.

Topics: Benzhydryl Compounds; Controlled Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Symptoms of urgency and increased frequency of micturition and nocturia, with or without urge incontinence, are the hallmarks of a condition that afflicts millions of Americans. Several new drug therapies, as well as behavioral approaches, provide keys to management.

Topics: Activities of Daily Living; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cost of Illness; Cresols; Female; Humans; Imipramine; Information Services; Male; Mandelic Acids; Mass Screening; Medical History Taking; Muscarinic Antagonists; Nurse's Role; Nursing Assessment; Patient Acceptance of Health Care; Patient Education as Topic; Phenylpropanolamine; Physical Examination; Prevalence; Quality of Life; Social Behavior; Tolterodine Tartrate; Urination Disorders

A few decades ago, urinary diversion, usually with an ileal conduit, was the ultimate outcome for most children with spina bifida. The revolutionary institution of clean intermittent catheterization has changed the algorithm totally. Furthermore many new drugs have been developed during the past decade and have decreased the need for surgery dramatically. In this article, we will focus on the most recent data on new modalities of therapy to help avoid urinary diversion or bladder augmentation.. In addition to clean intermittent catheterization and oxybutynin treatment, a new generation of anticholinergic medications, such as tolterodine, has been developed. For patients who drop out because of the side-effects of oral administration, new methods of administration are now available, including extended release and intravesical instillation. For those unresponsive, botulinum-A toxin and resiniferatoxin are two relatively new drugs in the field, administered as intravesical injection and instillation, respectively. Intravesical or transdermal electrical stimulation, sacral nerve stimulation and biofeedback therapy are under development, but as currently administered, are not yet completely successful.. Although life-saving in many respects, bladder augmentation introduces life-long risks of its own. Our goal in describing 'conservative' management is to prevent this step. Many alternatives to surgery are available now and more effective strategies are under development.

Topics: Anti-Dyskinesia Agents; Benzhydryl Compounds; Biofeedback, Psychology; Botulinum Toxins; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Diterpenes; Electric Stimulation Therapy; Humans; Infant; Infant, Newborn; Mandelic Acids; Meningomyelocele; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Catheterization

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Estrogen Replacement Therapy; Female; Humans; Mandelic Acids; Medical History Taking; Middle Aged; Muscarinic Antagonists; Nurse Practitioners; Nursing Assessment; Phenylpropanolamine; Physical Examination; Primary Health Care; Referral and Consultation; Toilet Training; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Administration, Intravesical; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Botulinum Toxins; Capsaicin; Cholinergic Antagonists; Cresols; Cystitis, Interstitial; Diterpenes; Humans; Mandelic Acids; Neurotoxins; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Diseases; Urination Disorders

Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.

Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urinary Incontinence

Overactive bladder (OAB) is a chronic, distressing condition characterised by symptoms of urgency (sudden overwhelming urge to urinate) and frequency (urinating more than eight times daily), with or without urge urinary incontinence (sudden involuntary loss of urine). It affects millions of people of all ages and both sexes world wide, with greater prevalence in women and the elderly. The treatment of OAB is aimed at reducing debilitating symptoms, which have a significant effect on all aspects of an individual's quality of life, including social, domestic, psychological, occupational, physical and sexual functioning. Anticholinergic agents are currently recommended as first-line therapy for OAB. Their use results in significant clinical improvement in patients, although a lack of selectivity for receptors in the bladder may lead to troublesome side effects, including dry mouth, blurred vision, somnolence, dizziness and constipation. Recent research efforts have focused on developing drugs with a reduced propensity for causing these problems. Of the available anticholinergic agents, oxybutynin and tolterodine are the most widely used to treat OAB. Studies directly comparing tolterodine immediate-release (IR) with oxybutynin IR have shown that the two agents have similar efficacy. However, tolterodine IR is significantly better tolerated, particularly with respect to the incidence and severity of dry mouth. An extended-release formulation of tolterodine (4 mg capsules) has recently been developed to allow for once-daily dosing. In addition to greater convenience, tolterodine extended-release has shown enhanced efficacy and tolerability compared with tolterodine IR.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

Overactive bladder (OAB), the symptom complex of urinary urgency and frequency with or without urge incontinence, affects the lives of millions of Americans. In recent years, more successful treatment options have emerged as advances have been made in understanding the pathophysiologic processes underlying OAB symptoms. However, because most therapeutic modalities for OAB are aimed at symptom resolution, rather than the treatment of distinct pathologic entities, a basic evaluation is required for all patients to establish whether existing (and treatable) pathologic processes are present. In the absence of these processes, symptom relief is both the objective and the outcome used to judge the efficacy of a specific modality. The type of therapy recommended for OAB may depend on several factors including age, existing behavioral patterns, estrogen status, degree of motivation, environmental surroundings, presence of other coexisting urinary symptoms, family support, and patient expectations. This article focuses on methods of identifying patients with OAB, and the role of developing strategies in treating this common disorder.

Topics: Aged; Algorithms; Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Quality Assurance, Health Care; Tolterodine Tartrate; United States; Urinary Incontinence

Tolterodine is the first muscarinic receptor antagonist that has been specifically developed for the treatment of overactive bladder. The objectives in the discovery program were to design a potent muscarinic receptor antagonist that is equipotent to oxybutynin in the bladder, but less potent in salivary glands, with the aim of improving tolerability (less dry mouth) in patients with overactive bladder. Tolterodine is non-selective with respect to the muscarinic M1-M5 receptor subtypes, but has a greater effect on the bladder than on salivary glands in vivo, in both animals and humans. Clinical results show that the efficacy and safety of tolterodine in overactive bladder is equal to that of oxybutynin, but that tolterodine is significantly better tolerated by the patients.

Topics: Animals; Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Diseases

To compare tolterodine with oxybutynin in treatment of urge incontinence.. A systematic review, following Cochrane methods, was performed to retrieve results of randomized trials that compared tolterodine with oxybutynin in adults with urge incontinence. Composite point estimates of efficacy (episodes of incontinence per 24-hour period, frequency, and voided volume) and safety (dry mouth, withdrawal, and dose modification) were calculated.. Four studies were included. Both drugs similarly decreased the number of micturitions in a 24-hour period. Oxybutynin was marginally superior to tolterodine in decreasing the number of incontinent episodes in a 24-hour period (weighted mean difference, 0.41; 95% confidence interval [CI], 0.04 to 0.77) and increasing the mean voided volume per micturition (8.24 mL; 95% CI, 14.19 to 3.38). Fewer patients had dry mouth (relative risk, 0.54; 95% CI, 0.48 to 0.61) and withdrew from the study because of side effects (relative risk, 0.63; 95% CI, 0.46 to 0.88) with tolterodine.. Oxybutynin and tolterodine share a clinically similar efficacy profile (although oxybutynin is statistically superior), but tolterodine is better tolerated and leads to fewer withdrawals as a result of adverse events.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

This analysis reviews clinical trials of the efficacy and safety of tolterodine for use in overactive bladder. It also compares the safety and efficacy of tolterodine and previously available pharmacotherapy. The MEDLINE database (1966 to present) was searched for all English language randomized controlled trials with keyword tolterodine. The search retrieved 10 randomized controlled trials involving tolterodine. Studies ranged from 2 to 12 weeks in duration. Nine trials studied tolterodine vs. placebo, 6 compared tolterodine vs. oxybutynin, 6 compared different doses of tolterodine, and 1 compared immediate-release and extended-release tolterodine. Doses of tolterodine were 0.5-4 mg bid or 4 mg extended-release daily, and doses of oxybutynin were 5 mg bid or tid. All studies found a benefit of tolterodine over placebo in decreasing symptoms of overactive bladder. Parameters significantly improved by tolterodine include number of voids per day, urine volume per void, number of incontinent episodes per day, pad use, maximal cystometric capacity, residual volume, volume at first detrusor contraction, and volume at normal desire to void. Tolterodine 2 mg bid was consistently of equal efficacy as oxybutynin 5 mg tid. Adverse events with both medications were mostly dose-related autonomic nervous system events. The most common adverse event was dry mouth, which was both more frequent and more severe with oxybutynin 5 mg tid than with tolterodine 2 mg bid. Dry mouth did not generally result in discontinuation of medication with either drug. Most drug withdrawal was because of blurred vision or headache. Tolterodine 2 mg bid caused less dose reduction, patient withdrawal, and adverse events, especially dry mouth, compared with oxybutynin 5 mg tid. A single trial found tolterodine extended-release 4 mg/day to have improved efficacy for decreasing urge incontinence episodes along with lower frequency of dry mouth vs. immediate-release tolterodine 2 mg bid. At 4 mg bid, tolterodine caused urinary retention. Neither drug significantly altered any laboratory tests, nor was there clear evidence of electrocardiographic abnormalities induced by either drug. In all randomized controlled trials to date, tolterodine 2 mg bid is an equally effective alternative to oxybutynin 5 mg tid, while causing less intense and less frequent dry mouth or need for treatment withdrawal.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Confidence Intervals; Cresols; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenylpropanolamine; Randomized Controlled Trials as Topic; Reference Values; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence, Stress

A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.

Topics: Benzhydryl Compounds; Benzofurans; Clinical Trials as Topic; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.

Topics: Benzhydryl Compounds; Budgets; Cholinergic Antagonists; Cost of Illness; Cost-Benefit Analysis; Cresols; Drug Costs; Humans; Mandelic Acids; Patient Compliance; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Continued developments in the understanding of lower urinary tract function have led to improvements in the pharmacologic manipulation of bladder dysfunction. Drug delivery changes have produced drugs that provide better efficacy and tolerability, thus improving patient compliance. Improvements in drug delivery systems have altered drug bioavailability and pharmacokinetics. Active current investigation in new agents and delivery systems for intravesical delivery has yielded intriguing early results that may substantially add to the armamentarium for the management of the overactive bladder (urgency, frequency, urge incontinence). New developments in the understanding of the neuropharmacology of the bladder, peripheral pelvic nerves, and sacral cord may provide agents with entirely new drug effects, either as primary agents or agents to be used in combination with currently available drugs. We herein review newer agents and drug delivery systems.

Topics: Adrenergic alpha-Antagonists; Aged; Animals; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Benzilates; Benzofurans; Calcium Channel Blockers; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Drug Administration Routes; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Muscle Relaxants, Central; Nortropanes; Phenylpropanolamine; Pyrrolidines; Tolterodine Tartrate; Urinary Incontinence

Tolterodine is a nonsubtype selective antimuscarinic agent recently approved as therapy in patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by muscarinic receptor blockade in the bladder wall and detrusor muscle. Despite short terminal disposition half-lives of 2-3 and 3-4 hours for tolterodine and its active 5-hydroxy metabolite, respectively, twice/day dosing is effective due to the drug's prolonged pharmacodynamic effects. Dosage adjustment is recommended in the presence of hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P450 2D6 and 3A4 isozymes. Tolterodine significantly reduces clinically relevant end points such as number of micturitions and number of incontinence episodes/day. In general, it is superior to placebo and equivalent to oxybutynin in this regard. As might be expected from its pharmacologic profile, the principal adverse effects of the drug are anticholinergic. In clinical trials, tolterodine was tolerated significantly better than oxybutynin. Its relative merits as a first- or second-line agent for patients intolerant of oxybutynin are unclear. Until pharmacoeconomic analyses are conducted that clearly justify use of this more expensive agent, tolterodine is perhaps best reserved for patients who are intolerant of or fail oxybutynin therapy.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Drug Evaluation; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.

Topics: Animals; Benzhydryl Compounds; Cholinergic Antagonists; Controlled Clinical Trials as Topic; Cresols; Half-Life; Humans; In Vitro Techniques; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

Urgency urinary incontinence afflicts many adults, and most commonly affects women. Medications, a standard treatment, may be poorly tolerated, with poor adherence. This warrants investigation of alternative interventions. Mind-body therapies such as hypnotherapy may offer additional treatment options for individuals with urgency urinary incontinence.. To evaluate hypnotherapy's efficacy compared to medications in treating women with urgency urinary incontinence.. This investigator-masked, noninferiority trial compared hypnotherapy to medications at an academic center in the southwestern United States, and randomized women with non-neurogenic urgency urinary incontinence to weekly hypnotherapy sessions for 2 months (and continued self-hypnosis thereafter) or to medication and weekly counseling for 2 months (and medication alone thereafter). The primary outcome was the between-group comparison of percent change in urgency incontinence on a 3-day bladder diary at 2 months. Important secondary outcomes were between-group comparisons of percent change in urgency incontinence at 6 and 12 months. Outcomes were analyzed based on noninferiority margins of 5% for between group differences (P < 0.025) (that is, for between group difference in percentage change in urgency incontinence, if the lower bound of the 95% confidence interval was greater than -5%, noninferiority would be proved).. A total of 152 women were randomized to treatment between April 2013 and October 2016. Of these women, 142 (70 hypnotherapy, 72 medications) had 3-day diary information at 2 months and were included in the primary outcome analysis. Secondary outcomes were analyzed for women with diary data at the 6-month and then 12-month time points (138 women [67 hypnotherapy, 71 medications] at 6 months, 140 women [69 hypnotherapy, 71 medications] at 12 months. There were no differences between groups' urgency incontinence episodes at baseline: median (quartile 1, quartile 3) for hypnotherapy was 8 (4, 14) and medication was 7 (4, 11) (P = .165). For the primary outcome, although both interventions showed improvement, hypnotherapy did not prove noninferior to medication at 2 months. Hypnotherapy's median percent improvement was 73.0% (95% confidence interval, 60.0-88˖9%), whereas medication's improvement was 88.6% (95% confidence interval, 78.6-100.0%). The median difference in percent change between groups was 0% (95% confidence interval, -16.7% to 0.0%); because the lower margin of the confidence interval did not meet the predetermined noninferiority margin of greater than -5%, hypnotherapy did not prove noninferior to medication. In contrast, hypnotherapy was noninferior to medication for the secondary outcomes at 6 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 75.0-100%; medications, 83.3% improvement, 95% confidence interval, 64.7-100%; median difference in percent change between groups of 0%, 95% confidence interval, 0.0-6.7%) and 12 months (hypnotherapy, 85.7% improvement, 95% confidence interval, 66.7-94.4%; medications, 80% improvement, 95% confidence interval, 54.5-100%; median difference in percent change between groups of 0%, 95% confidence interval, -4.2% to -9.5%).. Both hypnotherapy and medications were associated with substantially improved urgency urinary incontinence at all follow-up. The study did not prove the noninferiority of hypnotherapy compared to medications at 2 months, the study's primary outcome. Hypnotherapy proved noninferior to medications at longer-term follow-up of 6 and 12 months. Hypnotherapy is a promising, alternative treatment for women with UUI.

Topics: Adult; Aged; Female; Humans; Hypnosis; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Single-Blind Method; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence, Urge

To compare the heart rate increase side effect of different antimuscarinic drugs used in overactive bladder (OAB).. Overall 341 patients were consecutively randomized to take seven different antimuscarinic drugs between January 2014 and June 2016 at three institutions, and 250 patients who completed the follow-up visits were accepted into this study. Ninety-one patients who never came to visits were excluded. Drugs were classified into two groups as selective (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride) and non-selective (fesoterodine fumarate, tolterodine tartrate, trospium chloride and propiverine hydrochloride) antimuscarinic drugs. The cardiac pulse rates and the blood pressures were recorded during the baseline, first visit (1 week) and second visit (1 month). Data were compared for drugs and two groups (selective versus non-selective) by using ANOVA test.. Baseline characteristics were similar among the patients using different antimuscarinic drugs. Statistically significant increase in heart rate occurred in patients treated with non-selective antimuscarinic drugs compared to those treated with selective drugs (p < 0.001), and this increase was especially evident in patients treated with trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride (p < 0.001, 0.003, 0.011 and 0.37, respectively). There was no statistical difference for the other side effects.. Our results showed that heart rate significantly increased in OAB patients treated with non-selective antimuscarinic drugs. Trospium chloride, tolterodine tartrate, fesoterodine fumarate and propiverine hydrochloride seem to have the most unfavorable properties with regard to increased heart rate side effect when compared to the other antimuscarinic drugs (darifenacin hydrobromide, solifenacin succinate and oxybutynin hydrochloride).

Topics: Adult; Aged; Benzhydryl Compounds; Benzilates; Benzofurans; Blood Pressure; Female; Heart Rate; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Prospective Studies; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

The aim of this study was to evaluate the response of women over 45 years with overactive bladder and detrusor overactivity to a 12-week course of oxybutynin or tolterodine treatment.. A total of 301 eligible Iranian women were studied. In this double-blinded trial, data were analyzed from 3-day urinary diaries from before and after 12 weeks of treatment in which patients were randomly assigned to receive oxybutynin or tolterodine in recommended doses. Patients' convenience and the drugs' side-effects were assessed by a monthly clinical appointment. End-points were changed from baseline to week 12 in bladder-diary variables and all observed or reported adverse events. The effectiveness of each drug was studied using the paired t-test and improvement after treatment between the two groups was compared by independent t-test.. Mean improvements in the terms of urgency (P = 0.64) and urge incontinence (P = 0.75) showed an insignificantly larger score in patients who were treated by oxybutynin. Improvement in night-time urinary urgency and nocturia (41.2% and 54.3% vs 39.7% and 40.1% in oxybutynin vs tolterodine groups, respectively) were shown to be more improved by tolterodine in comparison to oxybutynin (P = 0.72 and 0.04 for night-time urinary urgency and nocturia, respectively). Discontinuation of treatment due to adverse events was not significantly different in the two groups.. Oxybutynin and tolterodine showed similar efficacy on daytime symptoms of overactive bladder and similar side-effects in perimenopausal patients. For patients with the chief complaint of nocturnal frequency, prescription of tolterodine is preferably suggested.

Topics: Aged; Double-Blind Method; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Tolterodine Tartrate; Urinary Bladder, Overactive

To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four- week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same  packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients.

Topics: Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Iran; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Syndrome; Tolterodine Tartrate; Urinary Bladder, Overactive

The study included 95 female patients of 65 to 74 years (average age 67,1 years), who previously (more than 6 months before this study) took a course of monotherapy with hydrochloride trospium in higher dosages with unstable or weak effect. In this study, all patients were divided into three groups and were treated with two antimuscarinic drugs. The majority of older women suffering from OAB and treatment-resistant taking one antimuscarinic drug in high doses showed a significant positive progress in a state by adding a second antimuscarinic agent. The received side effects do not exceed thereof in comparison with treatment with a single drug.

Topics: Aged; Benzhydryl Compounds; Benzilates; Cresols; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring; Drug Synergism; Drug Therapy, Combination; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urodynamics

The aim of this study is to evaluate the efficacy and the tolerability of three classic antimuscarinic drugs used in the treatment of over active bladder syndrome using clinical data and quality of life tests, and to evaluate the parameters affecting the success of these drugs.. A total of 90 patients with urge urinary incontinence were randomly allocated into three groups either to receive tolterodine (group A), trospium chloride (group B) or oxybutynin (group C). Urogenital distress inventory short form (UDI-6) and Incontinence impact questionnaire short form (IIQ-7) of the Turkish Urogynecology and Pelvic Reconstructive Surgery Association were performed to each patient before and after treatment to evaluate the effectiveness and tolerability of the antimuscarinic drugs. Adverse events were also recorded during treatment.. Improved urodynamic test values were recorded after 6 weeks of treatment in each group. Similarly, statistically significant differences were observed in UDI-6 and IIQ-7 test scores before and after treatment. Complete cure was achieved in 86 % of patients in group A; however, complete cure rates were 67 and 80 % in group B and C, respectively. Although, patients reported comparable tolerability against trospium chloride (77 %) and tolterodine (80 %), only 23 % of patients using oxybutynin considered the drug as tolerable. The most common side effect was dry mouth, followed by insomnia. Both dry mouth and insomnia was highest in group C (50 %). One patient (0.3 %) in group B and two patients (0.7 %) in group C reported that they did not want to continue to use the drug.. Antimuscarinic medications are very successful in the treatment of urge urinary incontinence; however, the success of treatment is not only limited to clinical improvement. Patients do not regard a drug as successful unless it is tolerable, easy to adapt to the daily life and improve the quality of life even it has very successful clinical outcomes.

Topics: Adult; Benzhydryl Compounds; Benzilates; Cresols; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urodynamics

To compare the efficacy and safety of tolterodine and oxybutynin in the treatment of idiopathic overactive bladder in children.. A total of 204 children with idiopathic overactive bladder were randomly divided into three groups (n=68 each): placebo, tolterodine-treated and oxybutynin-treated. The efficacy and safety were evaluated two weeks after treatment.. The effective rate was 25% in the placebo group, 89% in the tolterodine-treated group, and 92% in the oxybutynin-treated group. The effective rate in the two treatment groups was significantly higher than that in the placebo group (P<0.05). There was a similar efficacy between the two treatment groups. The incidence of adverse events in the tolterodine-treated group (28%) was significantly lower than that in the oxybutnin-treated group (57%) (P<0.05).. Tolterodine has a similar efficacy to oxybutynin in the treatment of idiopathic overactive bladder in children, with better safety in pharmacotherapy.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Using 2 anticholinergic medications simultaneously (10 to 30 mg oxybutynin, 4 mg tolterodine and/or 5 to 10 mg solifenacin) we optimized the medical therapy for children in whom single agent anticholinergic therapy failed. We evaluated efficacy, tolerability and safety.. Children with refractory overactive bladder and incontinence were included in a prospective, open label protocol. Study inclusion criteria were persistent symptoms on medical and behavioral therapy, absence of correctable neurological anomalies, and partial clinical and urodynamic responses on an optimal dose of 1 well tolerated, long acting anticholinergic. Patients were followed prospectively every 3 months. The primary end point was efficacy for continence and the secondary end points were tolerability and safety.. We enrolled 14 girls and 19 boys in the study, and followed 19 patients with neurogenic bladder and 14 with overactive bladder a minimum of 3 months. Mean age at enrollment was 12 years and double medication was given for a mean of 16 months (range 3 to 42). Mean +/- SD urodynamic capacity improved from 192 +/- 92 to 380 +/- 144 ml, no deterioration in compliance was noted and maximal contraction pressure decreased from 77 +/- 27 to 18 +/- 15 cm H(2)O. Continence improved in all patients, of whom 17 were dry, and 14 and 2 were significantly and moderately improved, respectively. No, mild and moderate side effects were reported by 12, 16 and 5 patients, respectively. In 3 of the 17 patients who voided greater than 20% post-void residual urine developed. Blood tests and electrocardiogram remained normal.. In children with refractory overactive bladder double anticholinergic therapy is an efficient and serious alternative to surgery. Patients and families were satisfied with this nonoperative, innovative approach.

Topics: Adolescent; Algorithms; Benzhydryl Compounds; Child; Cresols; Drug Therapy, Combination; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Urinary Bladder, Overactive

Studies have shown cognitive problems in adults treated with anticholinergics. It is unclear if children are also susceptible to anticholinergic adverse effects. This study evaluates the effects of long-acting oxybutynin and tolterodine on short-term memory and attention in children with urgency and urge incontinence.. Children with urgency or urge incontinence were recruited to take part in a prospective, randomized double-blinded placebo controlled trial using long-acting oxybutynin or tolterodine. Patients underwent a baseline test of their memory/recall ability and attention span using a standardized developmental/neuropsychological assessment tool. They were then randomized to either medication or placebo with retesting in 2 weeks, at which time they were crossed. They were retested after the second 2 weeks.. Fourteen children (9 boys and 5 girls), ranging in age from 5 to 11 (M = 7.7) participated in the study. Attention and memory scores increased over time in all children, however, the analyses showed no significant negative effects of anticholinergic medications on attention or memory. Indeed, though not statistically significant, trends were for improvement in test scores in both areas.. Our results in a double blinded cross-over trial suggest that long-acting oxybutynin and tolterodine do not have a deleterious effect on children's attention and memory. Other cognitive functions may be affected.

Topics: Attention; Benzhydryl Compounds; Child; Child Behavior; Cholinergic Antagonists; Cognition; Cresols; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Memory; Mental Recall; Neuropsychological Tests; Phenylpropanolamine; Prospective Studies; Time Factors; Tolterodine Tartrate; Urinary Incontinence, Urge

Patients with neurogenic bladder dysfunction demonstrate an insufficient treatment outcome under dosage-escalated monotherapy. With the objectives of continence and normalised bladder pressure, safe and tolerable non-invasive treatment alternatives were evaluated by using combined antimuscarinics.. Twenty-seven patients who were previously registered in a doubled antimuscarinics study were enrolled in this study. The patients demonstrated urodynamic-proven neurogenic bladder dysfunction with incontinence, reduced bladder capacity, and increased intravesical pressure, resulting from spinal cord injury (n=21); spinal cord dysplasia (myelomeningocele; n=3); multiple sclerosis (n=2), and viral encephalomyelitis (n=1). On the basis of the initial study treatment, they were allocated into three groups and treated with two antimuscarinics. Before enrollment, at 4 wk, and at 6 mo, patients underwent urodynamics and recorded bladder diaries, including side-effects.. In all three groups, significant changes were noted at the 4-wk follow-up. Incontinence events decreased from an average of 7 to 1 event per day. The average median bladder capacity (180-393 ml) and reflex volume (125-335 ml) increased; detrusor compliance also improved (average, 15-33 ml/cm H2O). Seven patients reported side-effects; two discontinued the successful treatment. Two other patients did not reach satisfactory amelioration of the detrusor dysfunction.. With combined high-dosage antimuscarinic medications, 85% of the patients who previously demonstrated unsatisfactory outcome with dosage-escalated monotherapy were treated successfully. The appearance of side-effects was comparable to that of normal-dosed antimuscarinics. Further studies are required to investigate the long-term pharmacological and physiological background of our findings.

Topics: Adolescent; Adult; Benzhydryl Compounds; Benzilates; Cresols; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Spinal Cord Diseases; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urodynamics

Early studies of extended-release oxybutynin in patients with overactive bladder used adjusted-dose regimens ranging from 5 to 30 mg/day to achieve an optimal balance of efficacy and tolerability. The safety and tolerability of extended-release oxybutynin at a fixed dose of 10 mg once daily (commonly prescribed in clinical practice) is reported using pooled data from 2 multicenter, randomized, double-blind, parallel-group trials with a similar study design. One study compared extended-release oxybutynin with immediate-release tolterodine 2 mg bid. The other study compared extended-release oxybutynin with extended-release tolterodine 4 mg qd. In total, 576 patients received extended-release oxybutynin, 399 received extended-release tolterodine, and 193 received immediate-release tolterodine. The incidence of adverse events (AEs) was similar in the three treatment groups (extended-release oxybutynin, 70%; extended-release tolterodine, 64%; and immediate-release tolterodine, 79%). The most common adverse event was dry mouth (extended-release oxybutynin, 29%; extended-release tolterodine, 22%; and immediate-release tolterodine, 33%). Other AEs occurring in more than 5% of patients in any treatment group included constipation, diarrhea, headache, urinary tract infection, pain, dyspepsia, and peripheral edema, with no apparent difference across treatment groups. Most AEs (>90%) were mild or moderate in intensity in all treatment groups. The proportion of patients who discontinued study medication due to AEs was 6.1, 4.8, and 7.8% in the extended-release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively. In total, 1.2, 1.0, and 1.6% of patients in the extended-release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively, discontinued study medication due to dry mouth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Interstitial cystitis is a condition with a poorly understood etiology and, consequently, various treatment options have been described in the literature, with a less than optimal outcome. The aim of this study was to examine the role of a combination of intravesical hydrocortisone and heparin, together with oral bladder sedatives and systemic triamcinolone, for the treatment of interstitial cystitis.. A total of 26 patients who were diagnosed as having interstitial cystitis were treated with weekly intravesical hydrocortisone (200 mg) and heparin (25,000 IU) in physiological saline for 6 weeks. In addition, they were given oral bladder sedatives such as oxybutynin or tolterodine. Ulcerative, refractory and recurrent cases were treated with intramuscular triamcinolone (40 mg) weekly for 6 weeks.. All patients experienced an improvement in symptoms within 48 h of their first intravesical instillation. While 19 patients (73%) experienced almost complete pain relief, five of the remaining seven patients improved with intramuscular triamcinolone. Frequency reduced from a mean of 23.2 to 10.9 voids per day and was acceptable in 21 patients (80%). Six patients (23%) had a relapse of symptoms in the form of pain and were treated satisfactorily by means of intramuscular triamcinolone. The mean duration of follow-up was 18.3 months.. A combination of intravesical hydrocortisone and heparin, along with oral bladder sedatives and systemic steroids, has been used with encouraging results in a small group of patients with interstitial cystitis.

Topics: Administration, Intravesical; Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Anticoagulants; Benzhydryl Compounds; Cresols; Cystitis, Interstitial; Drug Therapy, Combination; Female; Heparin; Humans; Hydrocortisone; Injections, Intramuscular; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Triamcinolone

Bladder discomfort related to intraoperative catheterization of urinary bladder is a distressing symptom and more so in patients awakening from anaesthesia. These symptoms are similar to symptoms of overactive bladder. Muscarinic receptor antagonists have been reported to be effective in the treatment of overactive bladder. This study was therefore undertaken to evaluate the efficacy of oxybutynin and tolterodine in preventing catheter related bladder discomfort.. Two hundred and thirty-four consecutive adult patients, ASA I and II, of either sex, undergoing elective percutaneous nephrolithotomy surgery requiring urinary bladder catheterization were randomized into three equal groups of 78 each. Group C (control) received placebo, Group O (oxybutynin) received oxybutynin 5 mg and Group T (tolterodine) received tolterodine 2 mg orally 1 h before surgery. After induction of anaesthesia patients were catheterized with a 16 Fr Foley's catheter and the balloon was inflated with 10 ml distilled water. The bladder discomfort was assessed at 0, 1, 2 and 6 h after patient's arrival in the post-anaesthesia care unit. Severity of bladder discomfort was graded as mild, moderate and severe.. Incidence of bladder discomfort observed in the control group was higher, i.e. 58% (45/78), compared with oxybutynin and tolterodine groups where it was 35% (28/78) and 33% (26/78), respectively (P<0.05). Significant reduction in the severity of bladder discomfort was also observed after oxybutynin and tolterodine therapy compared with control (P<0.05).. Pretreatment with either oxybutynin or tolterodine reduces the incidence and severity of catheter related bladder discomfort.

Topics: Adult; Anti-Infective Agents, Urinary; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Intraoperative Care; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nephrostomy, Percutaneous; Phenylpropanolamine; Postoperative Complications; Prospective Studies; Severity of Illness Index; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Catheterization; Urinary Incontinence

Treatment with anticholinergic agents is the mainstay of therapy for detrusor instability (DI), a chronic and morbid condition characterized by urge urinary incontinence. The aim of this study is to assess the effectiveness and tolerability of tolterodine and oxybutynin in children with DI.. A total of 60 children with DI were enrolled, 30 (14 male, 16 female, mean age 7.97+/-2.71 years) in the tolterodine group and 30 (12 male, 18 female, mean age 7.33+/-2.23 years) in the oxybutynin group. In this prospective study we reviewed data from 60 children followed for at least 6 months. All of the patients in the study population had a history of dysfunctional voiding. Urodynamic investigations were conducted in all of the patients before and after anticholinergic treatment. Episodes of urge urinary incontinence and adverse events were also evaluated.. Improvements in urge incontinence episodes were similar for the children who received tolterodine or oxybutynin. Improvements in the urodynamic parameters were also the same in the two groups. Adverse events were significantly lower in the tolterodine group (13 events in 13 patients) compared to the oxybutynin group (27 events in 20 patients; P=0.027).. Reductions in urge urinary incontinence episodes were similar with tolterodine and oxybutynin in children with DI. Side-effects were more common with oxybutynin. Treatment of children with DI with tolterodine shows significantly better tolerability and this may enhance children's compliance during long-term treatment.

Topics: Benzhydryl Compounds; Child; Child, Preschool; Cresols; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Urinary Incontinence

The efficacy and the tolerability of extended-release oxybutynin chloride, 10 mg daily, and extended-release tolterodine tartrate, 4 mg daily, in women with or without prior anticholinergic treatment for overactive bladder (OAB) were compared in a post-hoc analysis of data from the Overactive Bladder: Performance of Extended Release Agents (OPERA) trial. The patient population and study methods have been described previously (Diokno et al., for the OPERA Study Group, Mayo Clin Proc 78:687-695, 2003). Among the group with anticholinergic experience, extended-release oxybutynin was significantly more effective than extended-release tolterodine in reducing micturition frequency at last observation (p=0.052). Complete freedom from urge incontinence was reported by significantly more patients taking oxybutynin than tolterodine at last observation (23.6 vs 15.1%, p=0.038). In addition, among patients completing a full 12 weeks of oxybutynin treatment, significantly greater reductions were observed compared with those taking tolterodine on the primary efficacy variable, number of urge incontinence episodes (p=0.049), and the combined total of urge and non-urge episodes (p=0.012), although the differences between treatment groups were not significant at last observation. In the anticholinergic-naïve group, efficacy and tolerability outcomes were similar across treatments, except that oxybutynin was associated with a significantly lower frequency of micturition at last observation (p=0.035). No efficacy differences favoring tolterodine were observed, and tolerability of the treatments was comparable. Dry mouth (mostly mild to moderate in severity) was reported significantly more often among participants taking extended-release oxybutynin than extended-release tolterodine (32.2 vs 19.2%, p=0.004), but only among those with previous anticholinergic experience. Discontinuation rates were comparably low across groups. The results demonstrate the appropriateness of initiating treatment for OAB with extended-release oxybutynin, particularly in women presenting with incontinence.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Demography; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Patient Dropouts; Patient Participation; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge

To study the influence of oxybutynin, tolterodine or trospium chloride, anticholinergics used to treat bladder overactivity, on sleep and the cognitive skills of healthy volunteers aged > or = 50 years.. In a randomized, double-blind, placebo-controlled study with a crossover design, 24 healthy sleepers (12 men and 12 women) aged 51-65 years underwent polysomnographic recordings and cognitive tests in a sleep laboratory. Study medications were given as a single dose containing the total recommended daily dose.. There was a significant reduction in rapid-eye movement (REM) sleep of approximately 15% and a slightly (but not significantly) greater REM latency after oxybutynin and tolterodine than with placebo. After trospium chloride, REM duration and latency were comparable with placebo. There was no effect of the tested anticholinergics on cognitive and subjective sleep variables.. Individuals aged > or = 50 years had a more distinct impairment of REM sleep after oxybutynin and tolterodine than had young people, but the reduction in REM sleep did not reach a pathological degree in this single-dose study. There was no apparent impairment of concentration or cognitive function, but impairment of cognitive function and neuropsychological side-effects cannot be excluded, especially when elderly patients with impaired REM sleep from various psychiatric diseases (e.g. depression) and/or sleep disturbances are given oxybutynin or tolterodine in long-term treatment.

Topics: Aged; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cognition; Cresols; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Polysomnography; Sleep, REM; Tolterodine Tartrate

To evaluate the effects of tolterodine and oxybutynin on visual accommodation, pupillary diameter, intraocular pressure and tear secretion in women with overactive bladder.. One hundred and four eyes from 52 consecutive female patients (age range: 22-60 years) with a urodynamic diagnosis of overactive bladder were prospectively investigated. Patients with a history of ocular disease or surgery were excluded. The subjects were randomly assigned to one of two groups: Group I received 2 mg tolterodine bid and Group II received 5 mg oxybutynin tid. All patients were evaluated at baseline (day 0) and after 1 month of treatment (day 28) by an ophthalmologist who was blinded to the medication. At each time point, a complete ophthalmic examination was performed and accommodation amplitude (AA), and pupillary diameter (PD) in dim and bright light were recorded. As well, tear secretion was assessed based on tear film break-up time and Schirmer I-test results. Statistical comparisons were made using the chi-square test, Student's t-test and Mann-Whitney U-test, as appropriate.. Twenty-eight patients (56 eyes) received tolterodine and 24 patients (48 eyes) received oxybutynin. The mean ages of the two groups were similar (P = 0.523). After 4 weeks of treatment, AA was significantly lower in the oxybutynin treated group (P = 0.003, 95% CI 0.15, 0.62) whereas there was no significant change in AA in the tolterodine treated group (P = 0.155, 95% CI -0.042, 0.86). At day 28, PD in dim light was significantly larger in the tolterodine treated group (P = 0.031, 95% CI -0.82, -0.06), whereas no significant change in PD in dim light was noted in the oxybutynin treated group (P = 0.330, 95% CI -0.38, 0.18). Neither group showed a significant change in PD in bright light values on day 28 (P > 0.05 for both). In each group, the differences from day 0 to day 28 for intraocular pressure, and Schirmer-I results were insignificant (P > 0.05 for all). Both groups had significantly shorter tear film break-up time after 1 month of therapy (P = 0.014 (95% CI 0.47, 3.81) and P = 0.02 (95% CI 1.14, 4.61) for the tolterodine and oxybutynin treated groups, respectively).. Four weeks of standard-dose oxybutynin treatment in women with overactive bladder decreases AA significantly, whereas the same duration of standard-dose tolterodine does not have this effect. However, tolterodine seemed to affect PD in dim light. One month of treatment with either of these anticholinergic drugs shortens tear film break-up time significantly. Concerning ocular side-effects, tolterodine seems to offer an advantage over oxybutynin because it does not affect AA, however, the shorter tear film break-up time with both agents suggests potential problems for patients who already have dry eye.

Topics: Accommodation, Ocular; Adult; Benzhydryl Compounds; Cresols; Eye Diseases; Humans; Intraocular Pressure; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Pupil; Single-Blind Method; Tears; Tolterodine Tartrate; Urinary Incontinence; Visual Acuity

This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended-release formulations of oxybutynin and tolterodine. Forty-four healthy volunteers received each of 4 treatments in a 4-period crossover design. The treatments consisted of osmotically controlled extended-release oxybutynin chloride tablets at 10 mg/d or extended-release tolterodine tartrate capsules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N-desethyloxybutynin, or tolterodine and its active 5-hydroxymethyl metabolite, as appropriate. The AUCinfinity ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended-release oxybutynin but may alter those of extended-release tolterodine.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Area Under Curve; Benzhydryl Compounds; Cresols; Cross-Over Studies; Delayed-Action Preparations; Drug Interactions; Enzyme Inhibitors; Female; Half-Life; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Omeprazole; Phenylpropanolamine; Tolterodine Tartrate

The incidence, severity and tolerability of dry mouth was compared in 790 women with overactive bladder who were treated with extended-release oxybutynin chloride 10 mg/day or extended-release tolterodine tartrate 4 mg/day for 12 weeks in a multicenter, double-blind, parallel-group study. Dry mouth was the most common adverse event associated with treatment, with an incidence rate of 28.1% in the oxybutynin group and 21.6% in the tolterodine group (P = 0.039). The majority of dry mouth events were mild in both treatment groups. Severe dry mouth occurred in 1.5% and 0.5% of patients in the oxybutynin and tolterodine groups, respectively (P = 0.173). Seven patients on extended-release oxybutynin and 4 patients on extended-release tolterodine discontinued treatment due to dry mouth (P = 0.380). The results of this analysis showed that dry mouth was common with both treatments, but most events were mild; there was no difference in the rate of severe dry mouth or in the rate of withdrawal due to dry mouth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Overactive bladder (OAB) has a significant impact on a patient's health-related quality of life (HRQoL). This study assessed the HRQoL of Japanese OAB patients following 12 weeks' treatment with tolterodine extended release (ER) or oxybutynin. A total of 293 patients with symptoms of OAB were randomized for treatment with tolterodine ER 4 mg once daily (n=114), oxybutynin 3 mg three times daily (n=122) or a placebo (n=57). Treatment efficacy and safety assessments were made over the 12-week period. HRQoL was assessed using the King's Health Questionnaire (KHQ). Patients receiving tolterodine ER or oxybutynin showed a significant (P<0.05) improvement in the Incontinence Impact, Role Limitations and most other KHQ domains compared with the placebo. These changes in HRQoL corresponded with significant (P<0.05) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo. Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Health Status Indicators; Humans; Japan; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Incontinence

To compare tolterodine with oxybutynin and placebo in people with neurogenic detrusor overactivity.. Prospective, randomized, double-blind, crossover trial plus open-label comparative stage.. Ten participants with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis who used intermittent catheterization.. Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes per day, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each at self-selected doses (SSDs).. Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005) and reducing incontinence (P < 0.001), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity. The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05).. Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improving continence, but with less dry mouth. Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladder volumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effect in this population, but further studies are required.

Topics: Adult; Benzhydryl Compounds; Cresols; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Multiple Sclerosis; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Spinal Cord Injuries; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence; Xerostomia

In general, extended-release (ER) formulations are designed to prolong the duration of efficacy and reduce the adverse effects of a drug. These formulations often contain the entire daily dose in a single tablet. Therefore, failure of the ER mechanism not only diminishes the desired benefits, but may temporarily expose the patient to drug concentrations higher than those released from a conventional tablet. In this study we determined whether pH has an effect on drug release from the ER formulations of oxybutynin (OROS technology) and tolterodine (membrane coated beads) in vitro and in vivo.. In vitro studies were based on standardised dissolution experiments for each drug in media of different pH (artificial gastric fluid at pH 1.2, artificial intestinal fluid at pH 7.5, and water). In the two separate, identically designed in vivo studies, single doses of each drug were administered alone and with an antacid to male and female healthy volunteers aged 18-45 years. The randomised, crossover, open-label in vivo studies employed a validated assay to determine plasma concentrations of tolterodine and its metabolite 5-hydroxymethyl tolterodine (5-HM), or oxybutynin and its metabolite N-desethyloxybutynin.. The in vitro study showed similar slow and steady drug release from ER-oxybutynin in each pH medium, with 64-71% released after 12 hours. Drug release from ER-tolterodine was steady and slow in artificial gastric fluid, with 72.5% of drug released after 12 hours. However, drug release was much faster in artificial intestinal fluid and water, where 69.8% and 69.1%, respectively, of the drug was released within 4 hours. These in vitro results were consistent with the findings of the in vivo studies. In vivo, the pharmacokinetic profile (peak plasma concentration [C(max)] and area under the concentration-time curve) of ER-oxybutynin was similar after administration with or without antacid, whereas C(max) values of both tolterodine and 5-HM increased significantly when ER-tolterodine was administered with antacid (p < or = 0.017 vs ER-tolterodine alone).. Changes in pH affected the release of tolterodine from ER-tolterodine, while they had no effect on the release of oxybutynin from the proprietary ER technology used in ER-oxybutynin. The technology employed in ER formulations thus determines sensitivity of drug release to external factors.

Topics: Adolescent; Adult; Antacids; Benzhydryl Compounds; Cresols; Cross-Over Studies; Delayed-Action Preparations; Female; Humans; Hydrogen-Ion Concentration; Male; Mandelic Acids; Middle Aged; Phenylpropanolamine; Tolterodine Tartrate

To compare the efficacy of tolterodine and oxybutynin in the treatment of specific, according to their urodynamic grade of severity, populations with overactive detrusor.. In this open, randomized, two-way crossover study 128 women with urodynamically confirmed, idiopathic detrusor overactivity were recruited. Patients were categorized in 4 grades of severity groups, according to the characteristics of the first overactive detrusor contraction during filling cystometrogram: high volume-low pressure (grade-group I), high volume-high pressure (grade-group II), low volume-low pressure (grade-group III) and low volume-high pressure (grade-group IV). The primary outcome measure was average volume of voided urine per micturition.. 107 patients successfully completed the study protocol and were included in the analyses: 40 in group IV, 36 in III, 25 in II and 6 in group I. In groups IV and III both oxybutynin and tolterodine significantly increased the average volume of voided urine per micturition but the differences between the drugs were not significant (p > 0.05). In group II neither of the drugs achieved significant changes in the outcome measure (p > 0.05).. Tolterodine and oxybutynin are clinically equipotent in treating detrusor overactivity in specific severity groups of patients, although urodynamic effects are somewhat different.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Cross-Over Studies; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence; Urodynamics

We compare the tolerability and efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with nonneurogenic diurnal urinary incontinence and symptoms of overactive bladder.. Children with a history of diurnal urinary incontinence were arbitrarily assigned to extended release oxybutynin, immediate release tolterodine or long acting tolterodine. The dose was titrated until effective (onset of complete diurnal urinary continence), maximal recommended dosage was achieved or bothersome anticholinergic side effects developed. An independent observer recorded the dose used, anticholinergic side effects and efficacy of therapy (incidence of urinary frequency, urgency, posturing and urinary incontinence).. The study included 86 girls and 46 boys. There were no statistically significant differences among the 3 treatment groups regarding the presence of peripheral or central nervous system anticholinergic side effects. Extended release oxybutynin and long acting tolterodine were significantly more effective at reducing daytime urinary incontinence than immediate release tolterodine (p <0.01 and 0 <0.05, respectively). Extended release oxybutynin was significantly more effective then long acting tolterodine for complete resolution of diurnal incontinence (p <0.05).. Extended release oxybutynin and long acting tolterodine are more effective than immediate release tolterodine in decreasing diurnal urinary incontinence. Extended release oxybutynin chloride is more effective than either immediate or long acting tolterodine for control of daytime urinary incontinence and urinary frequency.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Dosage Forms; Female; Humans; Male; Mandelic Acids; Phenylpropanolamine; Retrospective Studies; Tartrates; Tolterodine Tartrate; Urinary Incontinence

To compare the efficacy and safety of an oxybutynin transdermal delivery system (OXY-TDS) and oral, long-acting tolterodine (TOL-LA) with placebo in previously treated patients with urge or mixed urinary incontinence.. After withdrawal of their current antimuscarinic therapy, 361 adult patients were randomized to 12 weeks of double-blind, double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day, daily TOL-LA 4 mg, or placebo. Evaluations included change from baseline in patient urinary diary symptoms, incontinence-specific quality of life, and safety.. OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes (median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo; P <0.05), increased the average void volume (median change 24 and 29 mL versus 5.5 mL, P <0.01), and improved quality of life (incontinence impact questionnaire [IIQ] total score, P <0.05; Urogenital Distress Inventory Irritative Symptom subscale, P <0.05) compared with placebo. The most common adverse event for OXY-TDS was localized application site pruritus (14% versus 4% placebo) accompanied by a low incidence of systemic side effects (eg, dry mouth 4.1%). Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment (dry mouth 7.3% versus 1.7% placebo, P <0.05).. OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence. OXY-TDS improves systemic safety with regard to anticholinergic side effects. Local skin irritation occurs in some OXY-TDS patients.

Topics: Administration, Cutaneous; Administration, Oral; Benzhydryl Compounds; Cresols; Dermatitis, Contact; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence, Stress

To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder.. The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated.. Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events.. Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.

Topics: Administration, Oral; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Diarrhea; Double-Blind Method; Female; Headache; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Salivation; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Tract Infections; Urination

Oxybutynin binds to the M(3) muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. The transdermal system delivers oxybutynin over a 3- to 4-day period after application to intact skin. Peak plasma concentrations of oxybutynin and the major active metabolite, N-desethyloxybutynin, are reached 24 - 48 hours after a single application and therapeutic concentrations are maintained throughout the dosage interval. In a large, randomised, double-blind trial, transdermal oxybutynin 3.9 mg/day significantly decreased the median number of incontinence episodes per week compared with placebo (-19 vs -15, p = 0.0165) in patients with overactive bladder. In addition, the micturition frequency was reduced and average voided volume was increased by transdermal oxybutynin treatment. Significant reductions in incontinence episodes following transdermal oxybutynin treatment were also observed in two further studies and the clinical efficacy was similar to that of oral tolterodine or oral oxybutynin. Transdermal oxybutynin was well tolerated in clinical trials. Application site reactions were the most common adverse effect; however, the majority were mild to moderate in severity. Adverse events associated with anticholinergic drugs (e.g. dry mouth) were less frequently reported in patients treated with transdermal oxybutynin than in those receiving orally administered oxybutynin or tolterodine.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Exanthema; Humans; Mandelic Acids; Middle Aged; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB).. Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed.. In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients.. Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urinary Incontinence; Urination

Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder. Patients and methods A randomized controlled trial was conducted at two urogynaecology centres in Hong Kong. In all, 106 women with urodynamically confirmed detrusor instability were recruited. Baseline severity assessments included a visual analogue scale (VAS), urinary diary and urinary pad-test. The women were randomized to receive either oral tolterodine 2 mg or oxybutynin 5 mg twice daily for 10 weeks. Treatment responses were assessed at 4 and 10 weeks using the VAS and urinary diary. Treatment tolerability was assessed at baseline, 4 and 10 weeks using the Xerostomia Questionnaire. A urinary pad-test was repeated at 10 weeks. Results The perceived change from baseline VAS was better in the tolterodine than the oxybutynin group after 10 weeks of treatment (per-protocol analysis, P = 0.043). The two drugs were effective in reducing the symptoms of frequency (P < 0.001). Tolterodine was significantly better than oxybutynin in reducing urinary leakage (urinary pad-test; median change - 5.00 g vs 0 g, P = 0.019). Both drugs caused a significant worsening of dry mouth (overall dryness, P < 0.005; discomfort, P < 0.005; sleep, P = 0.021; speaking, P = 0.045; swallowing, P = 0.004; and liquid consumption, P = 0.017). Conclusions Both oxybutynin and tolterodine were effective in ameliorating the severity of the symptoms of detrusor instability. Tolterodine was better than oxybutynin in both subjective and objective outcome measures, but both drugs caused similar worsening of dry mouth that may limit the tolerability of these medications.

Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Agonists; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.

Topics: Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urination

Tolterodine exhibits a favourable selectivity for the urinary bladder over salivary glands in vivo, in the anaesthetised cat, whereas oxybutynin shows the opposite selectivity profile in this model. This study further evaluated the selectivity profiles of tolterodine and oxybutynin by comparing the effects on bladder function and visual accommodation in the same individuals.. In a double-blind, randomised, four-way crossover study, 16 healthy volunteers received single oral doses of tolterodine 5 mg and oxybutynin 2.5, 5 and 7.5 mg. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision) at regular intervals.. A dose-dependent increase in maximum bladder capacity was observed for oxybutynin [2.5 mg (+35%), 5 mg (+45%) and 7.5 mg (%)]. The effect of tolterodine 5 mg on bladder capacity was approximately twice (+93%) that seen after oxybutynin 5 mg and the onset of the effect was more rapid with tolterodine. Effects on visual accommodation were also dose-dependent for oxybutynin (maximum changes in near point of vision were 13%, 20% and 29%, respectively). The maximum change observed after tolterodine 5 mg was the same as after oxybutynin 5 mg (i.e. 20%).. Tolterodine seems to exhibit selectivity for the bladder over the eye. Therefore, these results suggest that the normal dosage of tolterodine (2 mg twice daily) may have less effect on visual accommodation than the equivalent dosage of oxybutynin (5 mg three times daily) in patients with an overactive bladder.

Topics: Adult; Benzhydryl Compounds; Cresols; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eye; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder

This double-blind, multicenter study compared the efficacy and tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin (Alza, Palo Alto, USA) in Asian patients with overactive bladder.. Two-hundred-and-twenty-eight adults with overactive bladder symptoms were randomized to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n = 116). After 8 weeks' treatment, changes in micturition diary variables, patients' perception of treatment benefit, and tolerability endpoints were determined.. The mean (+/- SD) number of micturitions/24 h decreased by 2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment benefit was over 70% in each treatment group. Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients (55% vs 82%; P = 0.001). Dry mouth was reported by significantly fewer patients on tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin (10% vs 16%). There were no safety concerns.. Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder, and shows significantly better tolerability. This may enhance compliance during long-term treatment.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination

To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder.. The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline.. A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups.. Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nervous System Diseases; Phenylpropanolamine; Probability; Prospective Studies; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence, Stress; Urination Disorders; Xerostomia

We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland.. In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments.. Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment.. Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urination

Oxybutynin chloride and tolterodine tartrate are anticholinergic agents used to suppress involuntary bladder contractions in urinary incontinence. They act by inhibiting binding of acetylcholine to the muscarinic receptors in the detrusor muscle of the bladder. The same types of muscarinic receptors are found in the salivary glands; thus anticholinergic agents may decrease saliva production and cause dry mouth, a commonly cited reason for discontinuation of therapy.. The primary objective of this study was to compare saliva output, which is an objective measure of dry mouth, in subjects taking immediate- or extended-release oxybutynin, tolterodine, or placebo.. This was a single-site, single-dose, randomized, double-blind, 4-treatment, 4-period crossover study. Subjects were randomly assigned to 1 of 4 treatment sequences that included extended-release oxybutynin 10 mg, tolterodine 2 mg, immediate-release oxybutynin 5 mg, and placebo. Saliva output was measured objectively before dosing with each treatment and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing.. Thirty-six healthy adult volunteers (22 women and 14 men) participated in the study. They ranged in age from 19 to 42 years (mean, 27 years). Thirty-one were white, 3 Asian, and 2 black. There were no significant differences in predose saliva output between the 4 study groups. With placebo, saliva output increased throughout the day. Saliva output was maintained at predose levels throughout the day with extended-release oxybutynin. Two hours after dosing with tolterodine and immediate-release oxybutynin, saliva output decreased nearly 0.5 g in specimens collected over 2 minutes. All 3 active treatments were associated with lower saliva output compared with placebo. Extended-release oxybutynin and tolterodine were similar with respect to area under the saliva concentration-time curve but were associated with significantly greater saliva output than was immediate-release oxybutynin (P < 0.01). There were no serious adverse events (AEs) in this study. AEs were similar between treatments, although the incidence of headache was higher in the active-treatment groups than with placebo.. Objective assessment of saliva output in healthy adult volunteers indicated that extended-release oxybutynin and tolterodine had less impact on saliva output than did conventional immediate-release oxybutynin, suggesting that they may yield lower levels of dry mouth.

Topics: Adult; Area Under Curve; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Cross-Over Studies; Double-Blind Method; Female; Headache; Humans; Male; Mandelic Acids; Phenylpropanolamine; Saliva; Salivation; Tartrates; Tolterodine Tartrate

Antimuscarinic compounds are increasingly used to treat the symptoms of overactive bladder; however, their use is often restricted by peripheral adverse effects (AEs). On the other hand, data regarding their influence on the central nervous system (CNS) are limited. This randomized, single-blind, parallel-group quantitative-topographical EEG (qEEG) study of clinical phase I investigates the potential CNS adverse effects of the three antimuscarinic drugs--tolterodine, oxybutynin, and trospium chloride--in comparison to placebo. Overall, 4 x 16 (total 64) young, healthy male volunteers were included in the study. The subjects were given either placebo or the clinically recommended daily doses of the drugs dispensed in three doses on a single day (tolterodine 2 mg bid and once placebo, total 4 mg/d; oxybutynin 5 mg tid, total 15 mg/d; and trospium chloride 15 mg tid, total 45 mg/d). The qEEG was recorded prior to and up to 4 hours after each intake of the trial medication (a total of 10 qEEG sessions) under three different conditions: at rest with eyes open, eyes closed, and under mental demand. The drug tolerability was subjectively evaluated by the volunteer and the investigator. In comparison to placebo (10% confidence interval), tolterodine and trospium chloride did not induce changes of the qEEG power in five of the six frequency bands (i.e., delta, alpha 1, alpha 2, beta 1, and beta 2). Isolated power decreases were only observed in the theta frequency band. In contrast, oxybutynin caused significant power reductions in four frequency bands (theta, alpha 1, alpha 2, and beta 1; p < 0.01). The subjectively evaluated drug tolerability was comparable between all treatment groups, although differences in the AE occurrence existed, with the AE frequency being higher in the oxybutynin group. The results of this study support the findings that oxybutynin as a tertiary amine crosses the blood-brain barrier, causing significant qEEG activity changes and more pronounced central adverse effects. Although tolterodine is also a tertiary amine, it shows limited effects on qEEG activity (i.e., slight theta power reductions), comparable to the effects of trospium chloride, a quarternary amine, which barely crosses the blood-brain barrier. The minimal qEEG changes observed with tolterodine and trospium chloride reflect most probably a rebound message from the peripheral target organs. Prescription of oxybutynin thus implicates a higher risk of CNS side effects.

Topics: Adult; Benzhydryl Compounds; Benzilates; Central Nervous System; Cresols; Electroencephalography; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Placebos; Tolterodine Tartrate

This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination

To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder.. A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (> or = micturitions/24 h) and symptoms of urgency and/or urge incontinence (> or = 1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition.. After 12 weeks' treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n = 118) and oxybutynin (n = 118), respectively, and by 10.5% in those on placebo (n = 57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily.. Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.

Topics: Adult; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urination; Urination Disorders

To examine the safety, efficacy, and tolerability of tolterodine in four randomized, double-blind, parallel, multicenter, 12-week studies of patients with overactive bladder.. Two of the four studies compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily) and placebo, one study compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily), and one study compared two dosages of tolterodine (1 and 2 mg twice daily) to placebo. Efficacy was determined from micturition diaries and patient perception of their bladder condition. Safety and tolerability were assessed from adverse events and laboratory measures.. A total of 1,120 patients were randomized and treated at 134 centers. For the primary efficacy variable, the number of micturitions/24 hours, pooled results showed a significant decrease from baseline for the 1 mg tolterodine (P < 0.001), 2 mg tolterodine (P < 0.001), and 5 mg oxybutynin (P < 0.01) groups, compared to placebo. Both tolterodine doses and oxybutynin significantly decreased incontinence episodes/24 hours and significantly increased volume voided/micturition, compared to placebo. Tolterodine at a dose of 2 mg twice daily and 5 mg oxybutynin twice daily were significantly more effective in improving patient perception of bladder condition than placebo. Tolterodine at a dose of 2 mg and 5 mg oxybutynin were equivalent in their effectiveness. Tolterodine at doses of 1 mg and 2 mg were tolerated significantly better than oxybutynin when adverse events, dry mouth (both frequency and intensity), dose reductions, and patient withdrawals were considered.. Although oxybutynin is highly effective, its clinical utility is limited by systemic side effects that lead to frequent discontinuation of treatment or dose reductions. Patients receiving tolterodine should not experience these limitations and instead will get safe and long-term effective treatment for their condition.

Topics: Adult; Analysis of Variance; Benzhydryl Compounds; Chi-Square Distribution; Cholinergic Antagonists; Confidence Intervals; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Statistics, Nonparametric; Time Factors; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination

To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India.. s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed.. Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively.. Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Prescriptions; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

The differential risk of incident dementia associated with receiving various overactive bladder (OAB) drugs is unknown.. To estimate the association of antimuscarinic OAB drug (exposure), compared with a β-3 agonist (mirabegron), and incident dementia.. A population-based nested case-control study was conducted in patients treated with OAB medications in Ontario, Canada. A total of 11 392 patients aged ≥66 yr with a new diagnosis of dementia between 2010 and 2017, and 29 881 age- and sex-matched controls without dementia were included in the study.. Receipt of an antimuscarinic OAB drug or receipt of mirabegron, within the previous 6-12 mo.. Cases developed dementia and Alzheimer's disease. Controls were derived from the general population and matched to cases based on important baseline characteristics. Odds ratios (ORs) for incident dementia, adjusted for demographic and health-related characteristics, were determined.. Patients receiving solifenacin (OR 1.24; 95% confidence interval 1.08-1.43) and darifenacin (OR 1.30; 95% CI 1.08-1.56) in the prior 6 mo had increased odds of incident dementia compared with those receiving mirabegron. In the 6 mo to 1 yr prior to diagnosis, receipt of solifenacin (OR 1.34; 95% CI 1.11-1.60), darifenacin (OR 1.49; 95% CI 1.19-1.86), tolterodine (OR 1.21; 95% CI 1.02-1.45), and fesoterodine (OR 1.39; 95% CI 1.14-1.71) was associated with increased odds of incident dementia compared with receipt of mirabegron. No effect was seen with oxybutynin or trospium. Limitations included misclassification of the outcome and residual confounding associated with the use of health administrative databases.. Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron. Oxybutynin and trospium were not associated with dementia, likely due to a protopathic bias. Careful drug selection is warranted when treating patients with OAB.. In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.

Topics: Aged; Canada; Case-Control Studies; Dementia; Humans; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antidepressive Agents; Benzilates; Benzofurans; Brazil; Clinical Decision-Making; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Pyrrolidines; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Denmark; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Norway; Practice Patterns, Physicians'; Prospective Studies; Pyrrolidines; Registries; Solifenacin Succinate; Sweden; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Details on the therapeutic effects of long-term antimuscarinic therapy have not been reported. Thus, the aim of this study is to evaluate the detailed long-term therapeutic effect of antimuscarinic therapy.. All consecutive patients who visited the urologic outpatient clinics of a medical center for treatment of overactive bladder syndrome and received antimuscarinic therapy of 12 months or more were retrospectively reviewed. All medical records, including the Overactive Bladder Symptom score (OABSS), the modified Indevus Urgency Severity Scale and the International Prostate Symptoms score (IPSS) questionnaires, and uroflowmetry parameters were reviewed at each visit.. A total of 140 patients had received 12 months or more of antimuscarinic therapy. Sustained therapeutic effects were observed by persistent decreases of IPSS-storage score, IPSS-total score and OABSS score. Moreover, the maximum flow rate did not change over time. A temporary increase in postvoid residual volume and decrease in voiding efficiency were found, but these parameters improved over long-term visits. Side-effects were observed in 81 patients (57.9%) and included dry mouth (n = 58, 41.4%), constipation (n = 48, 34.3%) and blurred vision (n = 4, 2.9%); all side-effects were tolerable. Patients aged 75 years or more (n = 94) had a higher comorbidity rate (n = 46, 48.9%) before treatment but generally exhibited similar therapeutic effects as overall patients; elderly patients could also tolerate side-effects.. Sustained therapeutic effects were observed in patients who received 12 months or more of antimuscarinic therapy, even in elderly patients. In addition, side-effects in patients receiving long-term therapy were also common but tolerable.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Constipation; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Retrospective Studies; Severity of Illness Index; Solifenacin Succinate; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Vision Disorders; Xerostomia; Young Adult

Overactive bladder (OAB) is highly prevalent particularly among obese patients and significantly impacts quality of life. Anticholinergics are the first-line treatment. The effect of obesity on medication compliance has not been studied. Our study evaluated gender- and obesity-specific adherence and persistence of anticholinergic medications in OAB. We also compared adherence and persistence on solifenacin to oxybutynin, tolterodine, and all anticholinergics combined.. Truven Marketscan Commercial Claims and Encounter database from 2005 to 2013 was used. OAB patients aged 18-65 continuously enrolled for ≥12 months pre- and post-index were identified. Adherence was assessed by medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as number of days from anticholinergic initiation to discontinuation, switch, or end of study. Statistical analyses were performed using SAS 9.3.. Among 122 641 OAB patients, most common comorbidities were hypertension, depression, and diabetes; patients with these conditions were more compliant. Obese patients were 7% less likely to adhere and 6% more likely to become non-persistent on anticholinergics compared to non-obese. Males were 20% more likely to adhere to anticholinergics compared to females. Oxybutynin, solifenacin, and tolterodine were the most common anticholinergics. Solifenacin demonstrated higher adherence and persistence compared to all anticholinergics combined. The proportion of patients still on solifenacin at 1 year was 17.11%, compared to 12.64% for all anticholinergics combined.. Men are more likely to be adherent to anticholinergics than women. Obese patients are less likely to be compliant to medications, possibly related to severity of symptoms. Solifenacin had the highest rates of patient compliance.

Topics: Adolescent; Adult; Cholinergic Antagonists; Female; Humans; Male; Mandelic Acids; Medication Adherence; Middle Aged; Obesity; Quality of Life; Sex Factors; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Young Adult

This study aimed to evaluate the effects of intravesical instillation of the anticholinergic drugs oxybutynin, tolterodine, and trospium on bladder capacity and histopathological changes in the bladder mucosa.. The study included 20 male New Zealand white rabbits that were randomly allocated to four groups of five. In the oxybutynin, tolterodine, and trospium groups, the drugs used were 1 mg/kg of crushed tablet mixed with 5 mL of saline, instilled intravesically once per day for 4 weeks. The control group was administered only 5 mL of saline once per day for 4 weeks. Urodynamic measurement of the bladder was made before and after treatment. At the end of the treatment the animals were killed and the bladders were evaluated histopathologically.. There were no significant differences between pre- and post-treatment bladder capacity in any of the groups (P > 0.05). Histopathological evaluation showed that the mucosal epithelium was intact and there was minor inflammation in the control group and oxybutynin group (P > 0.05), whereas there was destruction of the mucosal epithelium and findings of diffuse inflammation in the tolterodine (P = 0.014) and trospium (P = 0.014) groups.. Intravesical oxybutynin treatment was observed to be safe; however, a single daily dose of oxybutynin may not be sufficient to increase bladder capacity. Intravesical use of trospium and tolterodine at high doses caused epithelial destruction and diffuse inflammation in the bladder mucosa. The irritation associated with epithelial destruction and inflammation prevented an increase in bladder capacity.

Topics: Animals; Benzilates; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Rabbits; Random Allocation; Tolterodine Tartrate; Urinary Bladder; Urological Agents; Urothelium

Real-world data on the pharmacological management of men who have lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are limited.. To characterize men with LUTS/BPH who had both storage and voiding symptoms and to evaluate treatment patterns in UK primary care.. This was an observational study of men aged ≥45 years with a diagnosis, symptoms or therapies indicative of LUTS/BPH with both storage and voiding components. These men were identified from the large Health Improvement Network (THIN) database between 1 January 2004 and 30 September 2011.. Drug prescriptions and switching/discontinuation patterns for α₁-blockers and antimuscarinics.. We identified 8694 men with a median age of 66.0 (interquartile range [IQR], 59.0-74.0) years. Most (7850; 90.3%) received an α₁-blocker, and 2167 (24.9%) received antimuscarinic therapy over a median of 2.1 years. The most commonly prescribed α₁-blocker was tamsulosin (81.8%); most frequent antimuscarinics were tolterodine (41.0%), oxybutynin (37.2%) and solifenacin (35.7%). Concomitant prescription of α1-blocker and antimuscarinic therapy (within 30 days of each other) was received by 1160 men (14.8% of α₁-blocker-treated men). Of α₁-blocker recipients, 3024 (38.5%) discontinued during follow-up, while 1149 (53.0%) discontinued antimuscarinic therapy. Of 2167 men who received an antimuscarinic, 476 (22.0%) switched to another antimuscarinic. Of the three most commonly prescribed antimuscarinics, solifenacin had the lowest proportions of discontinuations (43.0%) and switches (15.3%), and the longest median duration of therapy (90 days, IQR 30-300). General practice consultations accounted for most resource use (5307.9 per 1000 patient-years).. This study presents real-world management of men with LUTS/BPH who have both storage and voiding symptoms. The low proportion of men who received concomitant α₁-blocker and antimuscarinic therapy suggests that some patients are sub-optimally treated in routine clinical practice.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Benzhydryl Compounds; Cresols; Family Practice; Humans; Lower Urinary Tract Symptoms; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Primary Health Care; Prostatic Hyperplasia; Quinuclidines; Retrospective Studies; Solifenacin Succinate; Sulfonamides; Tamsulosin; Tetrahydroisoquinolines; Tolterodine Tartrate; United Kingdom

Incidences of overactive bladder (OAB) and cognitive dysfunction increase with aging. Treatment of OAB with antimuscarinic agents may result in cognitive decline, especially in patients with Alzheimer's disease (AD). The aim of this study is to evaluate the effect of antimuscarinic treatment on cognitive functions, depression, and quality of life (QOL) of patients with OAB.. This non-interventional prospective observational study was conducted in a geriatric medicine outpatient clinic. Overall, 168 OAB patients were enrolled. Patients were followed up in five groups: oxybutynin, darifenacin, tolterodine, trospium, and control groups. Follow-up visits were done at second, third, and sixth months. Comprehensive geriatric assessment, cognitive and mood assessment, QOL scales (IIQ-7, UDI-6) were performed.. Mean age of the patients was 73.5 ± 6.1. Of the 168 patients, 92.3% were female, 83.3% benefited from the treatment, and 37.1% discontinued the medication. Discontinuation rate and frequency of side effects were more frequent in the oxybutynin group. Mini Mental State Examination scores did not decline after treatment, even in AD patients. Geriatric Depression Scale scores, Activities of Daily Living scores, and QOL scores significantly improved after treatment.. Antimuscarinic agents are effective in OAB treatment. They have a positive impact on daily life activities, depression, and QOL indices. Furthermore, they do not have a negative effect on cognitive function in older adults with or without AD.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzilates; Benzofurans; Cognition Disorders; Cresols; Depression; Female; Follow-Up Studies; Geriatric Assessment; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) often present with voiding and storage symptoms, which may require combination therapy with an alpha blocker and an antimuscarinic (AM). This study compared treatment persistence in LUTS/BPH patients on alpha blocker monotherapy with those using combination alpha blocker and AM therapy (AB/AM).. Retrospective analysis of anonymized patient longitudinal prescription reimbursement claims data. All patients who had claims for any of four alpha blocker medications and six AM agents during an index period from April 1, 2011 to March 31, 2012 were included. For the combination therapy group, the effect of adherence with the AM medication on persistence to the alpha blocker was examined.. Patients on AB/AM combination therapy remained on alpha blockers for longer than those on alpha blocker monotherapy (p = 0.04); 92.4% were persistent at 3 months versus 89.0%, and at 1 year 50.8% were persistent versus 49.6%, respectively. The highest number of days on therapy was reported for tamsulosin plus solifenacin. As confirmed by multivariate analysis, patients with the highest adherence to AM medication (= 80%) persisted on alpha blockers for longer than those with the lowest (< 50%) adherence (p < 0.05).. Patients taking an AM in combination with an alpha blocker showed greater persistence with alpha blocker treatment over a 1 year period. When an AM is combined with an alpha blocker in patients with LUTS/BPH, the additional medication burden does not have a negative impact on persistence and may even improve it.

Topics: Administrative Claims, Healthcare; Adrenergic alpha-Antagonists; Aged; Benzofurans; Doxazosin; Drug Therapy, Combination; Humans; Longitudinal Studies; Male; Mandelic Acids; Medication Adherence; Middle Aged; Muscarinic Antagonists; Ontario; Prazosin; Prostatic Hyperplasia; Prostatism; Pyrrolidines; Quinazolines; Retrospective Studies; Solifenacin Succinate; Sulfonamides; Tamsulosin; Tolterodine Tartrate

To investigate patient satisfaction with antimuscarinic treatment of overactive bladder syndrome, and to identify factors having a significant influence on satisfaction.. A cross-sectional questionnaire survey was carried out to assess treatment satisfaction among male and female patients with overactive bladder (age ≥20 years) in the Hokuriku district of Japan. The overactive bladder symptom scores, treatment efficacies, adverse events (dry mouth and constipation), and patient satisfaction scores were investigated and compared among patients using different antimuscarinic therapeutics.. In total, 977 survey respondents (52.6% men; mean age 73.6 years) received antimuscarinic treatment. The mean overactive bladder symptom score of these patients was 6.17; in addition, 32.3% patients were satisfied with their treatment, but 33.1% were dissatisfied. Factors having a significant influence on treatment satisfaction were sex (men were less satisfied), efficacy, adverse events and the overactive bladder symptom score. Constipation negatively influenced patient satisfaction to a greater extent than did dry mouth. Patient satisfaction varied according to the drug used. Constipation was less severe with the immediate-release-type agents (imidafenacin and oxybutynin) than with the extended-release-type (propiverine, solifenacin or tolterodine).. Just one-third of Japanese Hokuriku patients with overactive bladder seem to be satisfied with their antimuscarinic treatment. Patient satisfaction is impaired by poor efficacy and the presence of adverse events; furthermore, constipation should be recognized as an adverse event that negatively influences patient satisfaction to a greater extent than dry mouth. Patient satisfaction differs according to the antimuscarinic agent used, with higher patient satisfaction being associated with less severe constipation.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Benzilates; Cresols; Cross-Sectional Studies; Female; Humans; Imidazoles; Japan; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Pediatric drug development is challenging when a product is studied for a pediatric disease that has a different underlying etiology and pathophysiology compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a therapeutic area with multiple unsuccessful development programs. The objective of this study was to critically evaluate clinical trial design elements that may have contributed to unsuccessful drug development programs for pediatric NBD. Trial design elements of drugs tested for pediatric NBD were identified from trials submitted to the U.S. Food and Drug Administration. Data were extracted from publically available FDA reviews and labeling and included trial design, primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of four products were identified. Although all four programs potentially provided clinically useful information, only one drug (oxybutynin) demonstrated efficacy in children with NBD. The lack of demonstrable efficacy for the remainder of the products illustrates that future trials should give careful attention to testing a range of doses, using objectively measured, clinically meaningful endpoints, and selecting clinical trial designs that are both interpretable and feasible. Compiling the drug development experience with pediatric NBD will facilitate an improved approach for future drug development for this, and perhaps other, therapeutic areas.

Topics: Adolescent; Adrenergic alpha-1 Receptor Antagonists; Area Under Curve; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Delayed-Action Preparations; Humans; Infant; Mandelic Acids; Marine Toxins; Muscarinic Antagonists; Oxocins; Phenylpropanolamine; Quinazolines; Tablets; Tolterodine Tartrate; Urinary Bladder, Neurogenic

To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the U.K. National Health Service (NHS).. A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a U.K. database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios.. Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs. 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY.. Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Topics: Benzhydryl Compounds; Cohort Studies; Cost-Benefit Analysis; Cresols; Humans; Incontinence Pads; Mandelic Acids; Markov Chains; Medication Adherence; Models, Economic; Muscarinic Antagonists; Patient Dropouts; Phenylpropanolamine; Quality-Adjusted Life Years; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; United Kingdom; Urinary Bladder, Overactive; Urinary Incontinence

The prevalence of overactive bladder (OAB) and Alzheimer's disease (AD) increases with age, and much attention has been paid to the risk of cognitive impairment which may be induced by antimuscarinics used for OAB in patients with AD. Imidafenacin, an antimuscarinic agent for OAB treatment, has been reported not to affect learning in normal animals. However, under the condition in which sensitivity to learning impairment by antimuscarinics is increased, it remains unclear whether imidafenacin still does not impair the learning. Therefore, the influences of imidafenacin on passive avoidance response were investigated in sham-operated and nucleus basalis of Meynert (nbM)-lesioned rats and compared with oxybutynin hydrochloride and tolterodine tartrate. The learning-inhibitory doses of intravenous oxybutynin hydrochloride and tolterodine tartrate were 0.3 and 3 mg/kg in sham-operated rats and 0.1 and 1 mg/kg in nbM-lesioned rats, respectively. Thus, the learning impairments by those antimuscarinics were more sensitive in nbM-lesioned rats than in sham-operated rats. On the other hand, intravenous administration of imidafenacin had no influence on learning in either case of the rats. In normal rats, however, intracerebroventricular administration of imidafenacin impaired learning to the same degree as that of oxybutynin hydrochloride. Thus, the present study suggests that imidafenacin, unlike the other antimuscarinics used, has no significant risk of enhancing learning impairment even in models whose sensitivity to learning impairment by antimuscarinics is commonly increased, probably because of its low brain penetration.

Topics: Animals; Basal Nucleus of Meynert; Behavior, Animal; Benzhydryl Compounds; Blood-Brain Barrier; Capillary Permeability; Cresols; Dose-Response Relationship, Drug; Imidazoles; Injections, Intravenous; Injections, Intraventricular; Learning; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Wistar; Reaction Time; Tolterodine Tartrate

Mirabegron, a selective β(3)-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Female; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Wistar; Thiazoles; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Neck Obstruction

To compare persistence of oxybutynin or tolterodine therapy among older patients newly prescribed one of these drugs.. We conducted a retrospective cohort study of Ontarians aged 66 years and older who were newly prescribed either drug between January 1, 2000 and December 31, 2007. Persistence with treatment was defined on the basis of refills for the drug within a grace period equal to 50% of the prescription duration.. We identified 31,996 patients newly treated with oxybutynin and 24,855 newly treated with tolterodine. After 2 years of follow-up, persistence on oxybutynin (9.4%) was significantly lower than that on tolterodine (13.6%, p < 0.0001). The median time to discontinuation of oxybutynin and tolterodine was 68 and 128 days, respectively.. Our findings suggest that the tolerability of these drugs differs substantially.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Databases, Factual; Drug Prescriptions; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Medication Adherence; Muscarinic Antagonists; National Health Programs; Ontario; Phenylpropanolamine; Proportional Hazards Models; Retrospective Studies; Tolterodine Tartrate; Urinary Incontinence, Urge

Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Aged; Benzhydryl Compounds; Cresols; Cystitis, Interstitial; Doxazosin; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate

To evaluate the efficacy of baclofen in combination with antimuscarinics to treat women with an overactive bladder (OAB) with abnormal voiding patterns.. An action research and chart review was conducted in 245 OAB women. Women were prescribed tolterodine or oxybutynin with or without baclofen after urodynamics. The complaint of voiding difficulty was followed up one week later.. There was a significant difference in the occurrence of voiding difficulty after antimuscarinic administration in OAB women with abnormal voiding patterns compared with normal patterns (18% vs 4.9%, respectively; p = 0.013). The clinical difference of voiding difficulty after treating with antimuscarinics between both voiding patterns disappeared after adding baclofen (abnormal voiding pattern vs normal pattern; 11.1% vs. 5.6%, respectively; p = 1.000).. Combined use of baclofen and antimuscarinic agents could reduce voiding difficulty in treating women with overactive bladders with abnormal voiding patterns.

Topics: Adult; Aged; Baclofen; Benzhydryl Compounds; Community-Based Participatory Research; Cresols; Drug Therapy, Combination; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive; Urination; Urodynamics; Young Adult

To compare the brain anticholinergic activities of five urinary spasmolytic drugs (USDs).. In vitro study.. Laboratory.. None.. A validated 96-well anticholinergic radio receptor bioassay using small incubation volumes (240 μL per well) was applied in the current study. The different USDs (tolterodine, oxybutynin, solifenacin, darifenacin, and 5-hydroxy-methyl-tolterodine (5-HMT; the active metabolite of fesoterodine) were dissolved in plasma in their respective therapeutic concentration ranges. The plasma samples were added directly to the wells of 96 filter plates, wherein the incubation, filtration, and counting of undisplaced radioactivity was performed. Standard curves with atropine were used as reference for estimations of anticholinergic activity (AA).. 5-HMT and tolterodine displayed the highest AA of the tested USDs. In the middle of the therapeutic concentration range, the central anticholinergic potency of 5-HMT and tolterodine was more than 10 times as high as that of oxybutynin, solifenacin, and darifenacin. Darifenacin exhibited the lowest AA at therapeutic serum concentrations (< one-third the AA of oxybutynin and solifenacin).. Tolterodine and fesoterodine appear to have the highest pharmacodynamic potential to induce central anticholinergic side effects of the tested USDs. Darifenacin displayed the lowest AA, and combined with a low degree of brain distribution, it has probably the most favorable pharmacological profile of the USDs with respect to risk of cognitive impairment in older adults.

Topics: Benzhydryl Compounds; Benzofurans; Biological Assay; Brain; Cognition Disorders; Cresols; Humans; In Vitro Techniques; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate

This study provides antimuscarinic agents for overactive bladder (OAB) display variable association with side effects mediated by the central nervous system (CNS), which may be of particular concern in the elderly. Adverse effects on CNS functioning are related to muscarinic receptor subtype selectivity and the ability of the agent to cross the blood-brain barrier, where P-gp plays a role in limiting permeability.. This study provides a parallel investigation of CNS penetration of antimuscarinic OAB agents in vivo and assessment of physical properties and permeability in cell monolayers in vitro. It adds further understanding of the roles of passive transcellular permeability and P-gp in determining CNS penetration of antimuscarinic OAB agents. It also enables a comparison of CNS side-effect profiles of OAB agents with preclinical CNS penetration data.. To assess and compare the mechanisms of central nervous system (CNS) penetration of antimuscarinic overactive bladder (OAB) agents.. Physical properties were computed or compiled from the literature. Rats were administered 5-hydroxymethyl tolterodine (HMT), darifenacin, oxybutynin, solifenacin, tolterodine or trospium subcutaneously. At 1 h postdose, plasma, brain and cerebrospinal fluid (CSF) concentrations were determined using LC-MS/MS assays. Brain and plasma protein binding were determined in vitro. Permeability in the presence and absence of the efflux transporter P-glycoprotein (P-gp) was assessed in RRCK and MDCK-MDR1 transwell assays.. Oxybutynin displayed extensive CNS penetration, with brain:plasma ratios (B:P), unbound brain:unbound plasma ratios (Kp,free) and CSF:free plasma ratios each >1. Tolterodine (B:P = 2.95, Kp,free = 0.23 and CSF:free plasma = 0.16) and solifenacin (B:P = 3.04, Kp,free = 0.28 and CSF:free plasma = 1.41) showed significant CNS penetration but with some restriction from CNS as indicated by Kp,free values significantly <1. 5-HMT, darifenacin and trospium displayed much lower B:P (0.03-0.16), Kp,free (0.01-0.04) and CSF:free plasma (0.004-0.06), consistent with poor CNS penetration. Permeability in RRCK cells was low for trospium (0.63 × 10(-6) cm s(-1) ), moderate for 5-HMT (11.7 × 10(-6) cm s(-1) ) and high for darifenacin, solifenacin, tolterodine and oxybutynin (21.5-38.2 × 10(-6) cm s(-1) ). In MDCK-MDR1 cells 5-HMT, darifenacin and trospium, were P-gp substrates, whereas oxybutynin, solifenacin and tolterodine were not P-gp substrates.. Brain penetration was low for antimuscarinics that are P-gp substrates (5-HMT, darifenacin and trospium), and significant for those that are not P-gp substrates (oxybutynin, solifenacin and tolterodine). CNS adverse events reported in randomized controlled clinical trials show general alignment with the preclinical data described in this study.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Benzhydryl Compounds; Benzofurans; Blood-Brain Barrier; Brain; Cell Line; Chromatography, High Pressure Liquid; Cresols; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Solifenacin Succinate; Tandem Mass Spectrometry; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

Both the physiological role of muscarinic receptors for bladder function and the therapeutic efficacy of antimuscarinic agents for overactive bladder syndrome are well documented. We investigated the effect of antimuscarinic agents with different subtype selectivity on urodynamic parameters in nonhuman primates and rodents and compared plasma levels of these agents between species. Anesthetized rhesus monkeys were transurethrally catheterized, and the bladder was infused with saline. Urodynamic parameters were measured before and after intravenous drug administration. Tolterodine (nonselective) and oxybutynin (moderately M(3)-selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M(3)-selective) were needed to increase the bladder capacity than those needed to decrease the micturition pressure. In rats, tolterodine had no effect on the bladder capacity but decreased the micturition pressure at all of the doses administered. Oxybutynin also decreased micturition pressure and increased bladder capacity at the highest dose. Plasma levels of these drugs overlap in both species. These results suggest that, in addition to the M(3) receptor, other muscarinic receptor subtypes contribute to regulate bladder storage function in nonhuman primates, since less subtype-selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure compared with M(3)-selective darifenacin. In addition, the role of muscarinic receptors in bladder storage function varies between primates and rodents. Compared with rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.

Topics: Animals; Benzhydryl Compounds; Cresols; Female; Macaca mulatta; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Species Specificity; Tolterodine Tartrate; Urinary Bladder

We compared the short-term risk of falls among recipients of oxybutynin or tolterodine to treat urinary incontinence.. We conducted a population based, retrospective cohort study with propensity score matching among patients 66 years old or older who commenced treatment with oxybutynin or tolterodine in Ontario, Canada. The primary outcome was a hospital visit for a fall within 90 days of drug initiation. Secondary outcomes included hospital visits for fractures, delirium or all cause mortality.. We found no difference in the risk of falls among users of oxybutynin vs tolterodine (adjusted hazard ratio 1.04, 95% CI 0.95 to 1.14). Secondary analyses revealed no differential risk of fractures (aHR 0.96, 95% CI 0.82 to 1.13) or delirium (aHR 0.90, 95% CI 0.66 to 1.23) associated with oxybutynin. However, statistically significant increases in the risk of all cause hospitalization (aHR 1.12, 95% CI 1.07 to 1.17) and death (aHR 1.20, 95% CI 1.07 to 1.35) were seen with oxybutynin.. Oxybutynin was not associated with a short-term increased risk of hospital visit for falls, fractures or delirium compared to tolterodine. Further research is needed to confirm whether oxybutynin is associated with an increased risk of hospitalization or death.

Topics: Accidental Falls; Aged; Benzhydryl Compounds; Cresols; Emergency Service, Hospital; Hospitalization; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Risk Factors; Tolterodine Tartrate; Urinary Incontinence, Urge

To investigate the effects of tissue stretch and muscarinic receptor stimulation on the spontaneous activity of the urothelium/lamina propria and identify the specific receptor subtype mediating these responses.. Isolated strips of porcine urothelium with lamina propria were set up for in vitro recording of contractile activity. Muscarinic receptor subtype-selective antagonists were used to identify the receptors influencing the contractile rate responses to stretch and stimulation with carbachol.. Isolated strips of urothelium with lamina propria developed spontaneous contractions (3.7 cycles/min) that were unaffected by tetrodotoxin, Nω-nitro-L-arginine, or indomethacin. Carbachol (1 μM) increased the spontaneous contractile rate of these tissue strips by 122% ± 27% (P < .001). These responses were significantly depressed in the presence of the M3-selective muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10-30 nM) but were not affected by the M1-selective antagonist pirenzepine (30-100 nM) or the M2-selective antagonist methoctramine (0.1-1 μM). Stretching of the tissue also caused an increase in the spontaneous contractile rate, and these responses were abolished by atropine (1 μM) and low concentrations of 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM). Darifenacin, oxybutynin, tolterodine, and solifenacin (1 μM) all significantly depressed the frequency responses to carbachol (1 μM).. The urothelium with the lamina propria exhibits a spontaneous contractile activity that is increased during stretch. The mechanism appears to involve endogenous acetylcholine release acting on M3 muscarinic receptors. Anticholinergic drugs used clinically depress the responses of these tissues, and this mechanism might represent an additional site of action for these drugs in the treatment of bladder overactivity.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzofurans; Carbachol; Cresols; Diamines; Mandelic Acids; Mucous Membrane; Muscarinic Antagonists; Muscle Contraction; Phenylpropanolamine; Piperidines; Pirenzepine; Pyrrolidines; Quinuclidines; Receptor, Muscarinic M3; Solifenacin Succinate; Stress, Mechanical; Swine; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urothelium

To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review.. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results.. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost-effectiveness ratio of > pound30,000/QALY threshold.. Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost-effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.

Topics: Benzhydryl Compounds; Benzilates; Cost-Benefit Analysis; Cresols; Decision Trees; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Child; Cresols; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Pediatrics; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive

To clarify the basic mechanism involved in the pathophysiology of cystitis by characterizing the urodynamic parameters, pharmacologically relevant (muscarinic and purinergic) receptors, and the in vivo release of adenosine triphosphate (ATP) in the bladder of hydrochloric acid (HCl)-treated rats.. The muscarinic and purinergic receptors in rat tissue were measured by radioreceptor assays using (N-methyl-³H) scopolamine methyl chloride ([³H]NMS) and αβ-methylene-ATP (2,8-³H) tetrasodium salt ([³H]αβ-MeATP), respectively. The urodynamic parameters and ATP levels were measured using a cystometric method and the luciferin-luciferase assay, respectively.. In the HCl-treated rats, the micturition interval and micturition volume were significantly (48% and 55%, respectively, P <.05) decreased and the number of micturitions was significantly (3.2-fold, P <.05) increased compared with those of the control rats. The maximal number of binding sites for [³H]NMS and [³H]αβ-MeATP was significantly (55% and 72%, respectively, P <.001) decreased in the bladder of HCl-treated rats, suggesting downregulation of both muscarinic and purinergic receptors. In the HCl-treated rats, the inhibition constant, K(i), values for oxybutynin, solifenacin, and darifenacin were significantly (1.3-1.4-fold, P <.05) increased, but those for tolterodine and AF-DX116 were unchanged. Similarly, the inhibition constant for A-317491, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium, and MRS2273 was significantly (5.5, 11, and 7.6-fold, respectively, P <.001) increased. Furthermore, the in vivo release of ATP was significantly (P <.05) enhanced in the HCl-treated rat bladder.. Both muscarinic and purinergic mechanisms might be, at least in part, associated with the urinary dysfunction due to cystitis.

Topics: Adenosine Triphosphate; Animals; Benzhydryl Compounds; Benzofurans; Cresols; Cystitis; Disease Models, Animal; Down-Regulation; Female; Hydrochloric Acid; Mandelic Acids; N-Methylscopolamine; Organophosphonates; Phenols; Phenylpropanolamine; Pirenzepine; Polycyclic Compounds; Pyridoxal Phosphate; Pyrrolidines; Quinuclidines; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Receptors, Purinergic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urination; Urodynamics

To assess if oxybutynin and tolterodine have an effect on simple reaction time in healthy volunteers.. Simple reaction time was evaluated before and 90 minutes after the oral administration of oxybutynin and tolterodine in a cross-over design. Twenty seven healthy volunteers, aged 26 to 48 years, were included in the study. The electromyographic activity of the flexor digitorum superficialis muscle that was used for the response was recorded, and premotor time was measured.. The mean age of the study group was 33.1 ± 7.4 years. Mean premotor times before oxybutynin and before tolterodine administration were statistically non-significant. Mean premotor times after the administration of oxybutynin and tolterodine were significantly longer than the initial premotor times (p = 0.003).. The results of the study showed that oxybutynin and tolterodine prolonged the simple reaction time. The prolonged simple reaction time may suggest a perceptive impairment. The potential for perceptive impairment as a side effect of oxybutynin and tolterodine might suggest a negative impact on the rehabilitation interventions and the activities of daily living because of central nervous system effects.

Topics: Administration, Oral; Adult; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Cross-Over Studies; Electric Stimulation; Electromyography; Female; Hand; Humans; Male; Mandelic Acids; Middle Aged; Muscle, Skeletal; Neuropsychological Tests; Phenylpropanolamine; Reaction Time; Reference Values; Tolterodine Tartrate

In modern drug discovery, numerous assay formats are available to screen and quantitate receptor-ligand interactions. Radioactive assays are "gold standard" because they are fast, easy, and reproducible; however, they are hazardous, produce radioactive waste, require special lab conditions, and are expensive on a large scale. Thus, it provides a lot of importance to the "mix & measure" assays that have an optical readout. Fluorescence techniques are likely to be among the most important detection approaches used for high throughput screening due to their high sensitivity and amenability to automation. The aim of the present study was to determine the functional antagonistic affinities of standard muscarinic antagonists in CHO cells over expressing m1, m3, and m5 receptors and to compare them with the respective binding affinities. This study was further extended to elucidate that Ca+2 measurement assays can serve as a functional screening tool for GPCRs. For this purpose, standard muscarinic receptor antagonists, namely, tolterodine, oxybutynin, and atropine were used. We determined and compared the IC50 values of these three standard inhibitors in fura 2 AM loaded m1, m3, and m5 overexpressing CHO cells and in radioligand binding assay. Both the assays exhibited comparable rank order potencies of the standard inhibitors. This study suggests that Ca+2 mobilization assays can be an alternate to radioligand binding assays.

Topics: Animals; Atropine; Benzhydryl Compounds; Calcium; CHO Cells; Cresols; Cricetinae; Cricetulus; Fluorescence; Fluorescent Dyes; Fluorometry; Fura-2; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Radioligand Assay; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Receptor, Muscarinic M5; Scopolamine Derivatives; Tolterodine Tartrate; Transfection

Topics: Benzhydryl Compounds; Child; Cresols; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Child; Cresols; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Benzhydryl Compounds; Child; Cresols; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

Antimuscarinic agents are the treatment of choice for overactive bladder syndrome. Due to the development of novel delivery systems, extended-release formulations of oxybutynin, tolterodine, and trospium chloride are now available. In addition to the convenience of once-daily dosing, the new formulations of these commonly prescribed agents have improved their therapeutic index, striking a better balance between efficacy and tolerability.

Topics: Benzhydryl Compounds; Benzilates; Chemistry, Pharmaceutical; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Overactive

The present study was undertaken to characterize in vivo muscarinic receptors in peripheral tissues (urinary bladder, submaxillary gland, colon, stomach, heart) of mice, and further to evaluate bladder-selectivity of anticholinergic agents to treat overactive bladder. Following i.v. injection of [3H]QNB in mice, the radioactivity in peripheral tissues was exclusively detected as the unchanged form. The in vivo specific [3H]QNB binding in particulate fraction of tissue homogenates of mice showed a pharmacological specificity which characterized muscarinic receptors. Binding parameters (Kd and Bmax) for in vivo specific [3H]QNB binding differed between mouse tissues. Oral administration of oxybutynin attenuated significantly in vivo specific [3H]QNB binding in all tissues of mice. From ratios of AUCurinary bladder/AUCother tissues of time-dependent muscarinic receptor occupancy, oral oxybutynin has been shown to exert little urinary bladder selectivity. Following oral administration of propiverine, there was a significant reduction of in vivo specific [3H]QNB binding in the urinary bladder, colon and submaxillary gland, but not in the stomach and heart. From the ratios of AUCurinary bladder to AUCsubmaxillary gland or AUCheart, it has been shown that oral propiverine exerts higher selectivity to muscarinic receptors in the urinary bladder than in the submaxillary gland and heart. Similarly, tolterodine displayed high selectivity to muscarinic receptors in the urinary bladder than in the submaxillary gland. Thus, the present study has demonstrated that [3H]QNB may be a useful ligand for in vivo characterization of muscarinic receptor binding of anticholinergic agents to treat overactive bladder. Propiverine and tolterodine have exhibited in vivo selectivity of muscarinic receptor in the mouse urinary bladder rather than in the submaxillary gland, and such receptor binding specificity may be the reason of lower incidence of dry mouth.

Topics: Administration, Oral; Animals; Area Under Curve; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Male; Mandelic Acids; Mice; Muscarinic Antagonists; Phenylpropanolamine; Protein Binding; Quinuclidinyl Benzilate; Receptors, Muscarinic; Time Factors; Tolterodine Tartrate; Urinary Bladder, Overactive

To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors (ChIs) and the bladder anticholinergics oxybutynin or tolterodine.. Prospective cohort study.. Nursing homes (NHs) in the state of Indiana.. Three thousand five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1, 2003, and December 31, 2004. Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine.. Indiana Medicaid claims data were merged with data from the Minimum Data Set (MDS). Repeated-measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale (MDS-COGS; scored 0-10) and change in activity of daily living (ADL) function using the seven ADL items in the MDS (scored 0-28). Potential covariates included age, sex, race, number of medications, and Charlson Comorbidity Index score.. Three hundred seventy-six (10.6%) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function, ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics (ChI alone), compared with 1.62 points per quarter when taking dual therapy, a 50% greater rate in quarterly decline in ADL function (P=.01). There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning.. In higher-functioning NH residents, dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone. The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use.

Topics: Activities of Daily Living; Aged; Alzheimer Disease; Benzhydryl Compounds; Cholinergic Antagonists; Cholinesterase Inhibitors; Cognition Disorders; Cohort Studies; Cresols; Drug Interactions; Drug Therapy, Combination; Female; Follow-Up Studies; Homes for the Aged; Humans; Male; Mandelic Acids; Neuropsychological Tests; Nursing Homes; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Pharmacotherapy constitutes an important adjunct to behavioral therapy for the treatment of overactive bladder (OAB). Tolterodine and oxybutynin are commonly prescribed drugs for OAB treatment that exert their beneficial effect by suppressing bladder muscle contractions. However, high discontinuation rates have been observed for these drugs in clinical trials, as well as in real-world settings, in part due to adverse effects. Extended-release (ER) formulations were introduced with an improved tolerability profile over immediate-release (IR) versions of the 2 drugs. No study has compared persistence and adherence to therapy for both the ER and IR versions of tolterodine and oxybutynin.. To compare persistence, adherence, and switch rates for the IR and ER formulations of oxybutynin and tolterodine for patients enrolled in a regional managed care plan.. Study patients were adults (aged e 18 years), with at least 1 pharmacy claim for either tolterodine extended-release (tol-ER), oxybutynin extended-release (oxy-ER), tolterodine immediate-release (tol-IR), or oxybutynin immediate-release (oxy-IR) during the period from July 1, 1999, to December 31, 2003, and were continuously eligible for benefits from 6 months before through 12 months after the initial OAB pharmacy claim (index) date. A retrospective cohort study design was used following patients from the index date to the occurrence of non-persistence with the index medication (i.e., a gap of > 45 days between successive prescription fills or a switch to any other OAB medication), or the end of a 1-year follow-up period, through December 31, 2004. Switching was defined as any change from the index medication, including a change in dose form (e.g., tol-IR to tol-ER), to one of the other 3 study drugs, or to a different OAB treatment (e.g., trospium chloride, oxybutynin patch, flavoxate, hyoscyamine sulfate, or propantheline bromide) during the follow-up period. Adherence was measured as the proportion of patients with a medication possession ratio (MPR) of at least 80%. MPR was calculated as (1) the sum of days supply for all pharmacy claims except the last pharmacy claim, divided by (2) the total number of days from the first fill date to the fill date of the last pharmacy claim. The association of drug therapy with study outcomes was assessed with bivariate and adjusted (multivariate) analyses. Multivariate analyses controlled for demographic and clinical characteristics, plan type, patient out-of-pocket cost for the index medication, and year of therapy initiation.. 1,117 patients had at least 1 pharmacy claim for an OAB study drug (n = 454 for tol-ER [40.6%], n = 249 for oxy-ER [22.3%], n = 306 for tol-IR [27.4%], n = 108 for oxy-IR [9.7%]), of whom 81.6% were women. The mean (standard deviation [SD]) age of the study population was 55.7 (14.5) years. Only 53.7% had at least 1 OAB diagnosis recorded during the 18-month eligibility period. 44.5% of patients did not have a refill after the initial (index) pharmacy claim (39.4% for oxy-ER, 42.7% for tol-ER, 46.1% for tol-IR, and 59.3% for oxy-IR; P = 0.004). Only 13.2% persisted with treatment for at least 1 year (tol-ER = 15.0%, oxy-ER = 15.3%, tol-IR = 11.4%, oxy-IR = 6.5%; P = 0.050). The median days to discontinuation (non-persistency) were 31.0 overall, 33.0 for tol-ER, 34.0 for oxy-ER, 32.0 for tol-IR, and 0 for oxy-IR; P = 0.010. The overall switch rate as a percentage of all study patients was 13.3%, ranging from 9.9% for tol-ER, 13.7% for tol-IR, 16.5% for oxy-ER, and 19.4% for oxy-IR; P = 0.020. Of patients who refilled their initial prescription at least once, 24.0% made a medication switch. Adherence rates as measured by percentage of patients with MPR >or= 80% were 30.3% overall and higher for the ER formulations: 35.2% for tol-ER, 36.1% for oxy-ER, 23.5% for tol-IR, and 14.8% for oxy-IR; P < 0.001.. Adherence was significantly better for ER than IR agents. The high rate of non-persistence (44.5%) following the first (index) prescription highlights the need for medication counseling by health care professionals.

Topics: Adult; Aged; Benzhydryl Compounds; Cohort Studies; Cresols; Databases, Factual; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Male; Managed Care Programs; Mandelic Acids; Middle Aged; Multivariate Analysis; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Retrospective Studies; Tolterodine Tartrate; Treatment Refusal; United States; Urinary Bladder, Overactive

Solifenacin succinate [YM905; (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the antimuscarinic properties of solifenacin and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin, propiverine and atropine. In radioligand receptor binding assay, Ki values of solifenacin for human muscarinic M1, M2, M3, M4 and M5 receptors were 26, 170, 12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pA2 value of 7.44+/-0.09. In these in vitro studies, the antimuscarinic action of solifenacin was more potent than that of propiverine and less potent than those of tolterodine, oxybutynin, darifenacin and atropine. In anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure. The dosages required to produce a 30% increase in maximum bladder capacity (ED30 values) of solifenacin and oxybutynin were 0.35 and 0.30 mg/kg i.v., respectively, indicating approximately equal efficacies. These results support the fact that solifenacin, similarly to currently used antimuscarinic agents, is an effective agent in the treatment of overactive bladder symptoms such as urinary frequency and urge incontinence.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzilates; Benzofurans; Binding, Competitive; Carbachol; CHO Cells; Cholinergic Agonists; Cresols; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Mandelic Acids; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; N-Methylscopolamine; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Muscarinic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Transfection; Urinary Bladder; Urinary Bladder, Overactive; Urination

We characterized muscarinic receptor binding in the mouse cerebral cortex after oral administration of anticholinergic agents used to treat overactive bladder.. Muscarinic receptors in the mouse cerebral cortex and bladder after oral administration of anticholinergic agents were measured using [(3)H]N-methylscopolamine.. In vitro binding affinities of tolterodine and its metabolite 5-hydroxymethyl metabolite in the mouse cerebral cortex and bladder were considerably greater than those of oxybutynin and darifenacin. Also, muscarinic receptor binding affinity of oxybutynin and its metabolite N-desethyl-oxybutynin in the cerebral cortex compared with that in the bladder was 2 to 3 times higher, whereas that of tolterodine and 5-hydroxymethyl metabolite was approximately 2 times lower. Oral administration of oxybutynin (76.1 micromol/kg), tolterodine (6.31 micromol/kg) and darifenacin (59.1 micromol/kg) showed binding activity that was approximately equal to that of bladder muscarinic receptors. Oral administration of oxybutynin (76.1 micromol/kg) showed significant binding of cerebral cortical muscarinic receptors in mice, as indicated by about a 2-fold increase in K(d) values for specific [(3)H]N-methylscopolamine binding 0.5 and 2 hours later. On the other hand, tolterodine and darifenacin given at oral doses that would exert a similar extent of bladder receptor binding activity as oxybutynin showed only a low level of binding activity of central muscarinic receptors in mice.. Significant binding of brain muscarinic receptors in mice was observed by the oral administration of oxybutynin but not tolterodine and darifenacin.

Topics: Animals; Benzhydryl Compounds; Benzofurans; Cerebral Cortex; Cresols; In Vitro Techniques; Male; Mandelic Acids; Mice; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Receptors, Muscarinic; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Overactive

The aim of this study was to describe a new experimental animal model for simultaneous measurement of carbachol-induced increase in intravesical pressure and salivary secretion in rabbits. Further, we also compared the in vivo potency and urinary bladder versus salivary gland selectivity profiles of Oxybutynin, Tolterodine, Solifenacin and Darifenacin. The intravesical pressure and salivary secretion were evoked by intra-arterial injection of carbachol (1.5 microg/kg). The carbachol-induced increase in intravesical pressure and salivation was simultaneously recorded before and after increasing doses of test drugs administered intravenously. The basal mean changes in intravesical pressure and salivation subsequent to carbachol administration were in the range of 6.7-7.5 mm Hg and 0.5-0.7 g respectively. Repeated administration of vehicle did not elicit any appreciable changes in intravesical pressure and salivary secretion to carbachol administration from the basal values till 3 h. All the test drugs exhibited a dose-dependent inhibition of carbachol-induced increase in intravesical pressure and salivary secretion. Darifenacin demonstrated a greater potency compared to other muscarinic receptor antagonists for inhibiting carbachol-induced increase in intravesical pressure. It also exhibited functional selectivity for the urinary bladder versus salivary gland. In contrast, Oxybutynin was functionally more selective in inhibiting carbachol-induced increase in salivary secretion. The observed urinary bladder versus salivary selectivity values were 0.6+/-0.2, 1.1+/-0.2, 1.7+/-0.5, and 2.3+/-0.5 for Oxybutynin, Tolterodine, Solifenacin and Darifenacin respectively. These results suggest that the functional selectivity of muscarinic receptor antagonists between urinary bladder and salivary glands can be readily detected in this model. Thus rabbits may represent a useful animal model for evaluating putative bladder selective muscarinic receptor antagonists for the treatment of overactive bladder.

Topics: Anesthesia; Animals; Benzhydryl Compounds; Benzofurans; Carbachol; Cholinergic Antagonists; Cresols; Injections, Intra-Arterial; Male; Mandelic Acids; Phenylpropanolamine; Pressure; Pyrrolidines; Quinuclidines; Rabbits; Salivary Glands; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder

The current study was undertaken to characterize the effects of oral administration of tolterodine on muscarinic receptor binding in the bladder and submaxillary gland and on salivation in mice. In the in vitro experiment, tolterodine and its metabolite (5-hydroxymethyl metabolite: 5-HM) competed concentration-dependently with [N-methyl-(3)H]-scopolamine ([(3)H]NMS) in the mouse bladder, submaxillary gland and heart, and the potencies of both agents were greater than that of oxybutynin. After oral administration of tolterodine (6.31, 21.0 micromol/kg) and oxybutynin (76.1 micromol/kg), there was a dose and time-dependent increase in K(d) values for specific [(3)H]NMS binding in the bladder, prostate, submaxillary gland, heart, colon and lung, compared with control values, suggesting significant muscarinic receptor binding in each tissue. The K(d) increase in each tissue by oral oxybutynin reached a maximum value of 0.5 h after oral administration and then rapidly declined, while that by tolterodine was greatest 2 h after the administration and it was maintained for at least 6 or 12 h, depending on the dose and on the tissue. Thus, muscarinic receptor binding of oral tolterodine was slower in onset and of a longer duration than that of oxybutynin. Also, oral oxybutynin showed relatively greater receptor binding in the submaxillary gland as compared with other tissues, but such high selectivity to the exocrine gland muscarinic receptors was not observed by oral tolterodine. Oral administration of tolterodine and oxybutynin reduced significantly the pilocarpine-induced salivary secretion in mice, and the attenuation of oral tolterodine appeared more slowly and it was more persistent than that of oral oxybutynin. The antagonistic effect of oral tolterodine on the dose-response curves to pilocarpine was significantly weaker than that of oxybutynin. These data suggest that oral tolterodine, compared with the case of oral oxybutynin, binds more selectively to muscarinic receptors in the mouse bladder than in the submaxillary gland, which may be advantageous in treating patients with overactive bladder.

Topics: Administration, Oral; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Male; Mandelic Acids; Mice; Mice, Inbred Strains; Muscarinic Antagonists; Myocardium; Phenylpropanolamine; Protein Binding; Receptors, Muscarinic; Salivation; Submandibular Gland; Tolterodine Tartrate; Urinary Bladder

To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity.. Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group).. Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case.. This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.

Topics: Administration, Intravesical; Analysis of Variance; Animals; Benzhydryl Compounds; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

The frequency, relative risk, resource utilization, and costs related to comorbidities associated with overactive bladder (OAB) were studied.. A retrospective analysis of patients with OAB who initiated treatment with tolterodine extended release (ER), oxybutynin ER, or oxybutynin immediate release (IR) between January 2001 and December 2002 was conducted to evaluate the frequency, relative risk, resource utilization, and costs related to three specific comorbidities associated with OAB: urinary tract infections (UTIs), depression, and fracture. Two patient cohorts (tolterodine ER versus oxybutynin ER and tolterodine ER versus oxybutynin IR) were matched on a 1:1 basis according to their propensity to receive a prescription for tolterodine ER.. The frequency and relative risk of UTIs were significantly lower in the tolterodine ER group than in the oxybutynin ER and oxybutynin IR groups. The relative risk of depression was also lower in the tolterodine ER group than the oxybutynin ER and oxybutynin IR groups; however, the differences were only significant in the tolterodine ER versus oxybutynin IR comparison. The utilization of UTI- and depression-related services and the number of antiinfective and antidepressant prescriptions were significantly lower in the tolterodine ER group than in the oxybutynin ER group. UTI- and depression-related costs were generally lower in the tolterodine ER group than in the oxybutynin ER or oxybutynin IR group.. Treatment of OAB patients with tolterodine ER was associated with reduced frequency, relative risk, medical and pharmacy resource utilization, and incurred costs related to selected OAB-associated comorbidities compared with treatment with oxybutynin ER or oxybutynin IR.

Topics: Benzhydryl Compounds; Comorbidity; Cresols; Delayed-Action Preparations; Depression; Female; Fractures, Bone; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Retrospective Studies; Risk; Tolterodine Tartrate; United States; Urinary Bladder, Overactive; Urinary Tract Infections

Topics: Adult; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To investigate the potential of antimuscarinic agents for sensory mechanisms in overactive bladder using intravesical instillation.. Antimuscarinic agents were instilled intravesically in rats using two protocols. In the high-dose protocol, 5 mg atropine, oxybutynin, and dimethindene (M2-selective muscarinic receptor antagonist) were instilled into the bladder, and cystometric parameters, such as bladder capacity, intercontraction interval, pressure threshold, and maximal voiding pressure were monitored. In the low-dose protocol, 0.1 and 0.5 mug/mL oxybutynin, trospium, tolterodine, and dimethindene were continuously infused into the bladder. The doses chosen were based on the calculated urine-excreted concentrations of trospium typically achieved from human oral treatment of 40 mg/day. The effect of carbachol with and without the low-dose agents was then assessed.. With the high-dose protocol, bladder capacity, intercontraction interval, and pressure threshold were increased when atropine and oxybutynin were instilled, but not when dimethindene was used. The maximal voiding pressure was not affected by any of the agents tested. In the low-dose protocol, none of the cystometric parameters were altered with antimuscarinic agents alone. The intercontraction interval decreased with intravesical carbachol (65% +/- 0.1% compared with baseline), but this was prevented with concomitant antimuscarinic agents.. We have separated the local inhibitory effects of antimuscarinic agents during the storage phase from a decrease in voiding pressure. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating overactive bladder, not only by suppression of muscarinic receptor-mediated detrusor muscle contractions, but also by blocking muscarinic receptors in bladder-afferent pathways.

Topics: Acetylcholine; Administration, Intravesical; Afferent Pathways; Animals; Atropine; Benzhydryl Compounds; Benzilates; Carbachol; Cresols; Dimethindene; Female; Infusions, Parenteral; Instillation, Drug; Mandelic Acids; Muscarinic Agonists; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Nortropanes; Phenylpropanolamine; Pressure; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Tolterodine Tartrate; Urinary Bladder; Urodynamics

To assess the clinical efficacy of tolterodine prescribed to children with non-neurogenic daytime urinary incontinence secondary to overactive bladder who had previously failed to improve with oral oxybutynin treatment and its relation to the side-effect profile and compliance status.. We evaluated 92 children presenting with daytime wetting, with or without nocturnal enuresis, who were receiving oral oxybutynin treatment. Children with chronic urinary tract infections, a neurologic lesion, an anatomic abnormality of lower urinary tract, voiding abnormality, and less than 1 year of oxybutynin treatment were excluded. Of the remaining 41 children (mean age 7.2 years, range 5 to 14 years), 30 agreed to switch to tolterodine and 11 continued receiving oxybutynin. Anticholinergic side effects, compliance, and clinical efficacy were assessed in the follow-up.. Of the 30 patients who switched to tolterodine, a complete response was in 18 patients (60%), partial improvement in 11 (37%), and no improvement in 1 (3%) after a mean of 14.4 months (range 12 to 16 months) of oxybutynin treatment. The anticholinergic side-effect score was 7.2, 9.3, and 11, respectively, for those with a complete response, partial improvement, and no improvement in the compliant group. The noncompliant group had the greatest side-effect score (16.9). The fairly compliant group had a side-effect score of 12.3. After a mean of 7.1 months (range 6 to 9 months) of tolterodine use, a complete response was reported in 24 patients and partial improvement in 5 (17%). In 1 patient, treatment failed completely. However, his side-effect score decreased from 11 to 2. All tolterodine users were compliant with treatment.. The results of this study in children with non-neurogenic daytime urinary incontinence have shown that tolterodine may increase the efficacy of pharmacotherapy, particularly in patients noncompliant to oxybutynin. Additional investigation of the anticholinergic side-effect scores and compliance tables is required to improve the clinical results of pharmacotherapy in incontinence due to overactive bladder in children.

Topics: Adolescent; Behavior Therapy; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Combined Modality Therapy; Cresols; Drug Evaluation; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Novel derivatives of Tolterodine (1) and Oxybutynin (2) have been designed using conformationally restricted azabicyclics as replacement for open-chain amines. The synthesis and structure-activity relationships are presented.

Topics: Animals; Benzhydryl Compounds; Binding Sites; Cresols; Drug Design; Mandelic Acids; Phenylpropanolamine; Rats; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Structure-Activity Relationship; Tolterodine Tartrate

This study was undertaken to compare the central nervous system (CNS) tolerability profiles of the extended-release formulations of oxybutynin chloride and tolterodine tartrate in the treatment of women with overactive bladder (OAB), as observed in the OPERA (Overactive bladder: Performance of Extended Release Agents) trial.. The OPERA trial was a randomized, double-blind, active-control comparison of the efficacy and safety of extended-release oxybutynin (10 mg/d) and extended-release tolterodine (4 mg/d) given to 790 women with OAB for 12 weeks. The incidence of reported CNS events was compared between the treatment groups by using the Fisher exact test.. The incidence of CNS adverse events was 9% and 8% for the oxybutynin and tolterodine treatment groups, respectively. The difference between groups was not statistically significant. All reported CNS adverse events were rated as mild or moderate in severity. There were no serious treatment-related adverse events in either group, and discontinuation because of a CNS adverse event was infrequent.. The extended-release formulations of oxybutynin and tolterodine were observed to be associated with a similar low incidence of CNS adverse events, which were mostly mild or moderate in severity.

Topics: Benzhydryl Compounds; Central Nervous System; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence

The management of chronic conditions, such as overactive bladder (OAB), is often limited by lack of patient adherence to medication. This article compares persistence rates among Medicaid patients who were prescribed 1 of 3 drugs for treatment of OAB: 2 long-acting agents with once-daily dosing, tolterodine tartrate extended-release capsules (tolterodine ER) and oxybutynin chloride extended release (oxybutynin ER), and oxybutynin immediate release (oxybutynin IR), requiring 3 tablets daily.. The study population was comprised of continuously enrolled Medicaid managed care patients filling prescriptions for tolterodine ER, oxybutynin ER, or oxybutynin IR between January 1, 2000, and December 31, 2003. Patients taking any OAB drug in the first 6 months of their observed period of enrollment were excluded to capture new users only. Using survival analyses adjusted for age, sex, and race, the rates of persistence by drug were analyzed. Possession time, the degree to which patients keep medication available even though they may not be taking it daily as prescribed, was also measured.. Of 1637 patients (75% women, 45% African American, 26% younger than 18 years of age), 182 were started on tolterodine ER, 215 on oxybutynin ER, and 1240 on oxybutynin IR. Only 32% of those taking oxybutynin IR and 44% of those taking either long-acting agent remained adherent past 30 days. Of those remaining after 30 days, the risk of nonadherence was higher for oxybutynin ER than for tolterodine ER (hazard ratio = 1.47; 95% confidence interval, 1.01-2.14).. Persistence rates are better for patients taking drugs with once-daily dosing, but there is a need for a better understanding of non-persistent patients.

Topics: Adolescent; Adult; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Medicaid; Middle Aged; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

To compare posttreatment medical costs for patients with overactive bladder (OAB) initiating treatment with oxybutynin chloride immediate release (oxybutynin IR), oxybutynin chloride extended release (oxybutynin ER), or tolterodine extended-release tartrate capsules (tolterodine ER).. Data were drawn from administrative claims of enrollees aged 18 years and older of a large US health plan. OAB patients were identified if at least 1 claim with an International Statistical Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for OAB appeared in medical claims from January 1, 2001, to December 31, 2002. The index prescription was assigned as the first filled prescription of oxybutynin IR (n = 3052), oxybutynin ER (n = 4503), or tolterodine ER (n = 7027) during the subject identification period. Medical costs over the year after initiation were calculated as a function of the health plan and member liability. Independent variables were treatment cohort, sex, age group, geographic region, baseline costs, specific OAB diagnosis codes, and comorbid illnesses. To compare medical costs across treatment cohorts, multivariate regressions correcting for potential selection bias were used.. Multivariate analysis results revealed that costs for patients taking oxybutynin IR were 48% higher than costs for patients taking tolterodine ER (P = .026), and costs for patients taking oxybutynin ER were 191% higher than costs for patients taking tolterodine ER (P <.0001). Adjusted medical costs were dollar 7486 for patients taking oxybutynin IR and dollar 14 766 for patients taking oxybutynin ER compared with dollar 5074 for patients taking tolterodine ER.. Differences in medical costs that remained after adjusting for patient characteristics suggest that treatment with tolterodine ER may be associated with lower medical care utilization after initiation of therapy for OAB.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Female; Health Care Costs; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Retrospective Studies; Selection Bias; Tolterodine Tartrate; United States; Urinary Incontinence

To examine levels of persistence and compliance as well as the economic impact of extended-release tolterodine (tolterodine ER) versus immediate- and extended-release oxybutynin (oxybutynin IR or oxybutynin ER) among commercially-insured patients with overactive bladder (OAB).. Patients with OAB who initiated tolterodine ER, oxybutynin IR, or oxybutynin ER between January 2001 and December 2002 were identified from the PharMetrics Patient-Centric database; the first medication used in this timeframe was used for treatment group assignment (ie, patients were only in 1 group). Exploratory assessment of persistency and compliance was conducted among all treated patients: subjects were matched 1:1 based on the estimated propensity score for tolterodine ER in remaining analyses. Measures included patient characteristics as well as levels of medication, outpatient and inpatient resource utilization, and costs. Primary comparisons were made descriptively; costs were evaluated using generalized linear models with a gamma distribution and log-link function.. Compliance did not differ between tolterodine ER (77.4%) and oxybutynin ER (74.3%), but was lower for oxybutynin IR (60.9%). Mean (+/- standard deviation) duration of therapy was higher for tolterodine ER (139 +/- 132 days) versus oxybutynin ER (115 +/- 122) and oxybutynin IR (60 +/- 85). Totals of 7257 and 5936 matched pairs were available for tolterodine ER versus oxybutynin ER and oxybutynin IR comparisons, respectively. The mean age was 54 years in all groups; the majority was women. Utilization of outpatient and inpatient medical services was consistently lower among tolterodine ER patients in both comparisons. Total costs were slightly lower for tolterodine ER versus oxybutynin ER (dollar 8303 +/- dollar 18 802 vs dollar 8862 +/- dollar 18 684) and oxybutynin IR (dollar 9975 +/- dollar 24860 vs dollar 10521 +/- dollar 22 602); differences were significant after multivariate adjustment.. Use of tolterodine ER results in comparable compliance to oxybutynin ER and longer duration of use relative to either form of oxybutynin. In addition, tolterodine ER may be cost-effective relative to oxybutynin IR or oxybutynin ER among commercially-insured persons with OAB.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Insurance Coverage; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

The objective of this study was to compare 1-year total healthcare costs for patients with overactive bladder (OAB) initiating treatment with extended-release formulations of tolterodine and oxybutynin: tolterodine tartrate extended-release capsules (tolterodine ER) versus extended-release oxybutynin chloride (oxybutynin ER).. A model was developed from the payer perspective using data from the PharMetrics Patient-Centric database. Monthly discontinuation rates were derived from a cohort of newly treated patients with OAB (tolterodine ER, n = 15 394 or oxybutynin ER, n = 7934). All were assumed to be receiving therapy for at least 1 month. Medical management costs were based on reimbursement for all services for a matched cohort of patients taking tolterodine ER and oxybutynin ER. Medical management costs for those discontinuing therapy were based on patients receiving OAB care without pharmacotherapy (n = 29 992). Drug costs were from AnalySource (December 2004).. After the 11-month follow-up period, 21% of patients taking tolterodine ER and 15% of patients taking oxybutynin ER remained on original therapy. One-year average total costs per patient for those started on tolterodine ER were dollar 8876 and dollar 9080 for oxybutynin ER, a difference of dollar 204 per year. Sensitivity analyses indicated results were robust to changes in drug cost and probability of discontinuation. When discontinuation rates were held equal, cost differences continued to favor tolterodine ER (21%, dollar 272/yr; 15%, dollar 233/yr).. Those taking tolterodine ER had lower monthly drug and medical management costs. This resulted in a total average annual cost savings of dollar 204 per patient for those started on tolterodine ER. At the end of 1 year, patients with OAB were more likely to remain on original drug treatment taking tolterodine ER versus oxybutynin ER.

Topics: Aged; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Health Care Costs; Humans; Mandelic Acids; Models, Theoretical; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity.. Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 microM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume.. Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar.

Topics: Animals; Benzhydryl Compounds; Cresols; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Tolterodine Tartrate; Urinary Bladder; Urinary Catheterization; Urinary Incontinence; Urination

To assess the reliability of symptom reports in 3-day vs 7-day bladder diaries used in clinical trials of patients with overactive bladder (OAB) and to compare those results and related issues with previous reports.. We analysed two large-scale, randomized, phase 3 clinical trials of the use of transdermal oxybutynin for treating patients with OAB. The first trial (Trial A, 520 patients) compared three doses of transdermal oxybutynin (1.3, 2.6 and 3.9 mg/day) with placebo. Patients documented their OAB symptoms in a 7-day diary. The second clinical study (Trial B, 361 patients) compared the efficacy of 3.9 mg/day transdermal oxybutynin with 4 mg/day extended-release tolterodine and with placebo; this trial required symptom recording for only 3 days. The internal consistency of the data from the 7-day trial was determined and then compared with the 3-day trial results.. Patients on transdermal oxybutynin or long-acting tolterodine for their OAB symptoms showed a clinically and statistically significant improvement, results that were documented in both 3-day and 7-day bladder diaries. However, compared with 7-day symptom records, 3-day diaries were associated with significantly better compliance with record-keeping (P < 0.001).. Seven-day diaries used in clinical trials supply accurate and reproducible data on clinical manifestations of OAB, but 3-day diaries are equally effective and have the potential for better accuracy through increased patient convenience. Three-day diaries may also reduce the tendency for patients to complete gaps in record-keeping from memory.

Topics: Benzhydryl Compounds; Chi-Square Distribution; Cresols; Humans; Mandelic Acids; Medical Records; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Time; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Incontinence

Topics: Accommodation, Ocular; Benzhydryl Compounds; Cresols; Eye Diseases; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Exercise; Female; Humans; Life Style; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Sex Factors; Tolterodine Tartrate; United States; Urinary Incontinence

We present our experience in the treatment of enuresis at the Pediatric Urology Outpatient Office over a period of four years. We report pertinent epidemiological data, diagnostic workup, as well as routine treatment protocol.. Between April 1998 and May 2002, 142 healthy children, aged between 6.5 and 18 years (mean: 9 +/- 0.5 years), were referred to us for bedwetting. Ninety three of them were boys and 49--girls. Eight of them had also concurrent daytime enuresis. According to our protocol, the type of enuresis was identified (primary or secondary) and then we administered the respective treatment. Sixteen children underwent behavioural therapy only. Fifteen children with detrusor instability received oxybutinine or tolterodine. Twenty children with diurnal and nocturnal enuresis were given desmopressin and oxybutinine or desmopressin and tolterodine. The remaining 91 children received monotherapy with desmopressin (individualized dose). The initial follow up ranged from 3 to 6 months.. Out of 111 children receiving desmopressin, 66 stopped wetting, but 28 relapsed in two weeks and treatment continued for 3 more months. Nine children became dry. In the other groups there was almost complete response to treatment.. Enuresis continues to be a suppressed problem for both children and parents; however, effective treatment is possible.

Topics: Adolescent; Antidiuretic Agents; Behavior Therapy; Benzhydryl Compounds; Chi-Square Distribution; Child; Combined Modality Therapy; Cresols; Deamino Arginine Vasopressin; Drug Therapy, Combination; Enuresis; Female; Greece; Humans; Male; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome

We investigated the effects of the new muscarinic receptor antagonist solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] and the current antimuscarinic drugs for the treatment of overactive bladder (oxybutynin, tolterodine and darifenacin) on intracellular Ca(2+) mobilization in response to M(3) muscarinic receptor activation in bladder smooth muscle and submandibular gland cells isolated from Cynomolgus monkeys. Solifenacin concentration-dependently inhibited carbachol-induced Ca(2+) mobilization, with affinity constant values (pKi) of 8.5 +/- 0.053 in bladder smooth muscle cells and 8.2 +/- 0.051 in submandibular gland cells (n = 5). The pKi value of solifenacin was almost equivalent to the values of oxybutynin, tolterodine and darifenacin in bladder smooth muscle cells (8.7, 8.5 and 8.4, respectively), while being lower than those in submandibular gland cells (9.0, 8.7 and 8.8, respectively). The bladder-selectivity index (Ki ratio: submandibular gland/bladder) for solifenacin (2.1) was statistically higher, moreover, than those for oxybutynin, tolterodine and darifenacin (0.51, 0.65 and 0.46, respectively). These findings consequently indicate solifenacin's unique profile in terms of its selectivity for bladder smooth muscle cells over salivary gland cells in non-human primates, relative to oxybutynin, tolterodine and darifenacin. Solifenacin may, therefore, confer a promising therapeutic advantage for reducing adverse effects, such as dry mouth, exhibited by current antimuscarinic therapy for overactive bladder.

Topics: Animals; Benzhydryl Compounds; Benzofurans; Calcium; Calcium Signaling; Carbachol; Cresols; Dose-Response Relationship, Drug; In Vitro Techniques; Inhibitory Concentration 50; Macaca fascicularis; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Submandibular Gland; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder

Overactive bladder (OAB) is a condition characterized by urgency, increased frequency of micturition, or urge incontinence. It affects a considerable segment of the population, particularly with increasing age. Pharmacotherapy is one of the most common approaches to the treatment of OAB.. This article describes the development and results of a model comparing health-economic outcomes for the new extended-release (XL) formulation of oxybutynin and immediate-release (IR) tolterodine in a population of community-dwelling Canadian adults with OAB.. A Markov model was developed to compare health-economic outcomes over the course of 1 year. Effectiveness and treatment-persistence data were derived from the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) trial, a 3-month comparison of oxybutynin XL 10 mg and tolterodine IR 4 mg, and were used, together with data from the literature (identified through a MEDLINE search of articles published between 1990 and 2003), to project outcomes beyond the trial period. Severity-specific cost profiles for incontinence were developed. In the principal analyses, cost items were limited to drug therapy, physician visits, use of pads or other protection, and laundry costs. Costs are reported in 2002 Canadian dollars.. Costs after 1 year were estimated to be an average of $32 less per patient for oxybutynin XL compared with tolterodine IR, and 3.1 additional patients in every 100 who received oxybutynin XL were expected to attain complete continence compared with those who received tolterodine. During the course of 1 year, patients receiving oxybutynin XL were expected to have a mean 16.5 additional incontinence-free days compared with those receiving tolterodine IR. The results were sensitive to relative drug prices. In the other sensitivity analyses, however, oxybutyrin XL maintained its advantage over a wide range of inputs.. The results of these analyses suggest that when priced equivalently, oxybutynin XL would reduce costs and provide better results than tolterodine IR over 1 year of treatment.

Topics: Benzhydryl Compounds; Canada; Costs and Cost Analysis; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Markov Chains; Middle Aged; Models, Economic; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases

To develop a short version of the King's Health Questionnaire (KHQ), as there is a practical need to have a shorter version to summarize the eight domain scores into fewer domains.. Data from 293 patients were obtained from a randomized, double-blind, placebo-controlled clinical trial in Japan of oxybutynin and tolterodine in patients with symptoms of an overactive bladder. The KHQ has two single-item and six multiple-item domains. To construct the short form of the KHQ one item was selected from the each of multiple-item domains, based on standardized structural coefficients estimated by confirmatory factor analysis (CFA) in a previous study. These six items include the domains: 'daily activities from role limitation', 'travel from physical limitation', 'social life from social limitation', 'family life from personal relationship', 'depressed from emotion' and 'tired from sleep and energy'. Based on the six selected items a series of psychometric analyses were conducted.. Exploratory factor analysis (EFA) with promax rotation identified two factors 'limitation of daily life' (LDL) and mental health. LDL consisted of 'daily activities', 'travel' and 'social life', and mental health included 'family life', 'depressed' and 'tired'. Based on the results from the EFA, the second-order factor structure was tested by CFA. The model fitted the data well for both the male and female model. The KHQ short form showed excellent reliability with Cronbach's alpha coefficients for LDL and mental health for both genders. The domains in the short form were responsive to clinical efficacy variables, and had statistically significant sensitivity to change in the patients' perception of bladder condition in all domains.. These analyses confirm the psychometric properties and clinical validity of the short-form KHQ, which appears to offer a practical, valid and reliable health-related quality-of-life instrument.

Topics: Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Surveys and Questionnaires; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

Solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the in vitro and in vivo bladder selectivity profile of solifenacin over salivary gland in the same animal species, and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin and atropine. Solifenacin and the other antimuscarinic drugs inhibited carbachol-induced increases in intracellular Ca(2+) levels in bladder smooth muscle cells and salivary gland cells isolated from rats in a concentration-dependent manner. The inhibitory effect of solifenacin for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57). In contrast, the inhibitory effects of the other antimuscarinic drugs for bladder smooth muscle cells were 1.7- to 2.2-fold more potent than those for salivary gland cells. In anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited functional selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland. Tolterodine was also 2.2- to 2.4-fold more selective in inhibition of bladder response. In contrast, oxybutynin, darifenacin and atropine did not show functional selectivity for urinary bladder. These results indicate that solifenacin exerts greater selectivity for urinary bladder over salivary gland than tolterodine, oxybutynin, darifenacin and atropine, and may consequently provide symptomatic benefit in the treatment of overactive bladder with less dry mouth than currently used antimuscarinic drugs.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzofurans; Calcium; Cresols; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Mandelic Acids; Muscarinic Antagonists; Myocytes, Smooth Muscle; Organ Specificity; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Rats; Rats, Wistar; Solifenacin Succinate; Submandibular Gland; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder

Oxybutynin and tolterodine are two drugs widely used for the management of overactive bladder and urge urinary incontinence. The once-daily, extended-release formulations benefit from being well tolerated and efficacious. However, their costs, compared with generic immediate-release (IR) oxybutynin, are significantly greater. This study compared the cost effectiveness of oxybutynin extended-release (Oxy-XL), tolterodine extended-release (Tol-ER), tolterodine immediate-release (Tol-IR) and oxybutynin immediate-release (Oxy-IR).. A cost-effectiveness model.. A systematic review that identified appropriate randomised clinical trials provided evidence on efficacy. Empirical models of drug effects (number of incontinent-free weeks) and persistence (proportion of patients still on therapy) were constructed in order to determine clinical effectiveness which was combined with cost data (direct medical costs to the UK NHS, year 2001 values) to calculate the drugs' cost-effectiveness from the perspective of the NHS. Univariate sensitivity analyses were conducted to test the robustness of the results.. Hypothetical cohort of patients with urge incontinence associated with overactive bladder.. The incremental cost per incontinent-free week for Oxy-IR (versus no treatment) ranged from pound sterling 2.58 to pound sterling 16.59. Oxy-XL and Tol-ER were more effective than Oxy-IR but at additional costs per incontinent-free week. Tol-IR did not appear to be a cost-effective option as it was less effective and more costly than the extended-release formulations. Uncertainty surrounding the health and cost consequences of early discontinuation affected these results, although the model results were robust to parameter uncertainty.. Oxy-IR, Oxy-XL and Tol-ER appear to be cost-effective options for the management of urge incontinence from the NHS perspective. A decision among the treatments depends on the acceptable cost per additional incontinent-free week.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Delayed-Action Preparations; Drug Costs; Female; Humans; Male; Mandelic Acids; Middle Aged; Models, Economic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride.. We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire.. The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients.. Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Cross-Over Studies; Enuresis; Female; Humans; Infant; Male; Mandelic Acids; Phenylpropanolamine; Prospective Studies; Tartrates; Tolterodine Tartrate; Treatment Failure; Urinary Incontinence

Topics: Adrenergic Uptake Inhibitors; Behavior Therapy; Benzhydryl Compounds; Benzilates; Biofeedback, Psychology; Cholinergic Antagonists; Contraindications; Cresols; Deamino Arginine Vasopressin; Electric Stimulation Therapy; Female; Humans; Imipramine; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Physical Therapy Modalities; Renal Agents; Tolterodine Tartrate; Urinary Incontinence; Urinary Incontinence, Stress

Topics: Administration, Cutaneous; Administration, Oral; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Xerostomia

Topics: Benzhydryl Compounds; Child; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Dosage Forms; Humans; Mandelic Acids; Phenylpropanolamine; Research Design; Retrospective Studies; Tartrates; Tolterodine Tartrate; Urinary Incontinence

Topics: Administration, Cutaneous; Administration, Oral; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Salivation; Tolterodine Tartrate; Treatment Outcome; United States; Urinary Incontinence; Urination

Topics: Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Geriatric Assessment; Geriatric Nursing; Humans; Mandelic Acids; Muscarinic Antagonists; Nurse's Role; Nursing Assessment; Nursing Homes; Phenylpropanolamine; Prevalence; Toilet Training; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder Diseases; Urination Disorders

Direct comparison of experimental data for drugs commonly used in the treatment of overactive bladder is difficult because of possible species differences. In this study, we compare the effects of atropine, propiverine, oxybutynin and tolterodine in strips of pig, guinea pig and mouse detrusor muscle. In the three species, we observed slight differences in potency of carbachol-induced biphasic contractile responses between the species (guinea pig>pig>mouse). Cumulative concentration-response curves for carbachol were shifted to the right by atropine, propiverine, oxybutynin and tolterodine. However, at higher concentrations of the latter three antagonists, the maximum response to carbachol was also reduced. Therefore, propiverine, oxybutynin and tolterodine must have additional pharmacological actions beyond competitive antagonism at muscarinic receptors. Electric field stimulation (30 Hz) of detrusor strips led to contraction amplitudes, which remained constant over time (210 min) in pig, decreased by 17+/-5% in guinea pig, and increased by 28+/-9% in mouse detrusor muscle. Electric field stimulation-evoked contractions were suppressed to 18% of pre-drug control by high concentrations of atropine (10 microM) in pig, but to a much lesser extent in guinea pig and mouse (to 46% and 70%, respectively). In all three species, a myogenic component of contraction was observed in the presence of tetrodotoxin (1 microM). Compared to atropine, the bladder spasmolytic agents propiverine, oxybutynin and tolterodine also reduced electrically evoked contractions in the three species, though higher concentrations were required. The differences in the reported effects of the spasmolytic agents commonly used for treating overactive bladder suggest that drug action is strongly dependent on the species. Thus, a comparison of drug effects is only feasible in the same animal model and the results cannot easily be transferred to humans.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzilates; Carbachol; Cholinergic Agonists; Cholinergic Antagonists; Cresols; Dose-Response Relationship, Drug; Electric Stimulation; Female; Guinea Pigs; In Vitro Techniques; Male; Mandelic Acids; Mice; Mice, Inbred C57BL; Muscle Contraction; Muscle, Smooth; Phenylpropanolamine; Species Specificity; Swine; Tolterodine Tartrate; Urinary Bladder

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Humans; Mandelic Acids; Phenylpropanolamine; Tartrates; Tolterodine Tartrate; Urinary Bladder Diseases

Topics: Adrenergic alpha-Antagonists; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Deamino Arginine Vasopressin; Humans; Imipramine; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Renal Agents; Tolterodine Tartrate; Urinary Incontinence

The etiologies and forms of congenital neuropathic bladder are described: contractile (25%), acontractile (15%), and intermediate (60%). The terminology relating to neuropathic bladder is defined and the principles of bladder management are highlighted: (1) must achieve a bladder that can fill at low pressure, (2) must achieve a bladder that can store urine at low pressure, (3) must achieve sphincter resistance that is sufficient to allow urine storage, and (4) must put in place a mechanism of achieving complete voluntary bladder emptying. The approach to investigation is set out in a logical sequence, and the methods of achieving the goals highlighted above are described. All of this is put in the context of managing the handicapped patient as a whole. It also is stressed that the aim is not just to achieve continence but perhaps even more importantly to protect renal function.

Topics: Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Female; Humans; Infant; Male; Mandelic Acids; Meningomyelocele; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Catheterization

Topics: Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Physical Therapy Modalities; Tolterodine Tartrate; United States; Urinary Incontinence

1. Muscarinic cholinoceptors (MChR) in freshly dispersed rat salivary gland (RSG) cells were characterized using microphysiometry to measure changes in acidification rates. Several non-selective and selective muscarinic antagonists were used to elucidate the nature of the subtypes mediating the response to carbachol. 2. The effects of carbachol (pEC(50) = 5.74 +/- 0.02 s.e.mean; n = 53) were highly reproducible and most antagonists acted in a surmountable, reversible fashion. The following antagonist rank order, with apparent affinity constants in parentheses, was noted: 4-DAMP (8.9)= atropine (8.9) > tolterodine (8.5) > oxybutynin (7.9) > S-secoverine (7.2) > pirenzepine (6.9) > himbacine (6.8) > AQ-RA 741 (6.6) > methoctramine (5.9). 3. These studies validate the use of primary isolated RSG cells in microphysiometry for pharmacological analysis. These data are consistent with, and extend, previous studies using alternative functional methods, which reported a lack of differential receptor pharmacology between bladder and salivary gland tissue. 4. The antagonist affinity profile significantly correlated with the profile at human recombinant muscarinic M(3) and M(5) receptors. Given a lack of antagonists that discriminate between M(3) and M(5), definitive conclusion of which subtype(s) is present within RSG cells cannot be determined.

Topics: Alkaloids; Animals; Atropine; Benzhydryl Compounds; Benzodiazepinones; Binding, Competitive; Biosensing Techniques; Carbachol; Cholinergic Agonists; Cresols; Diamines; Dose-Response Relationship, Drug; Furans; Male; Mandelic Acids; Muscarinic Antagonists; Naphthalenes; Phenethylamines; Phenylpropanolamine; Piperidines; Pirenzepine; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Submandibular Gland; Tolterodine Tartrate

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Female; Headache; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urination Disorders; Xerostomia

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Contraindications; Cresols; Glaucoma, Angle-Closure; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenylpropanolamine; Prospective Studies; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

The objectives of this study were to determine age- and gender-specific drug treatment prevalence rates for overactive bladder (OAB), and to compare resource use and costs among MCO members receiving drug treatment for OAB. Administrative claims data from seven affiliated health plans were analyzed for 8,661 members with a diagnosis or treatment indicative of OAB during 1998. Resource use and associated costs were analyzed over a four-month follow-up. In 1998, the prevalence of OAB among plan members was 1.1%. Of the patients with OAB, 71% did not receive pharmacotherapy. After multivariate analysis, treatment with tolterodine, oxybutynin, or other OAB treatment did not significantly affect the percent change in total per patient per month (PPPM) costs compared with the group not receiving a pharmacologic agent. Although the adjusted percent change in PPPM pharmacy costs was significantly higher within the tolterodine group, medical and total PPPM costs were not.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Comorbidity; Cost of Illness; Cresols; Female; Health Care Costs; Humans; Insurance Claim Reporting; Longitudinal Studies; Male; Managed Care Programs; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Retrospective Studies; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Evidence-Based Medicine; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Statistics as Topic; Tolterodine Tartrate; Urinary Incontinence

Tolterodine is a novel muscarinic receptor antagonist for the treatment of overactive bladder.. The purpose of this study was to examine the cost-effectiveness of tolterodine for patients with urge incontinence (UI) who discontinue initial therapy with oxybutynin in a Canadian setting.. We compared 2 treatment strategies for the management of adult patients with UI: (1) generic oxybutynin with no further treatment for patients who discontinue and (2) generic oxybutynin with switch to tolterodine (2 mg BID) for patients who discontinue. We developed a 1-year Markov model (4-week cycle length) with transitions between disease states of normal, mild, moderate, and severe. Transition probabilities over 12 weeks were obtained from randomized trial data, and drug discontinuation rates were obtained from Quebec prescription claims data. Outcome measures were time in "normal" health state and quality-adjusted life-years (QALYs) using EuroQol-5D utility scores from a survey of Swedish patients with overactive bladder. Costs to the health care payer and patient out-of-pocket costs (in Canadian dollars) were included.. For patients who discontinue oxybutynin, the use of tolterodine is associated with approximately 6 months per year in a normal health or mild disease state, compared with approximately 3 months for those who do not receive further drug therapy after discontinuation. Tolterodine use resulted in an annual additional cost per patient of Can $163. The incremental cost per QALY was Can $9,982 and appeared to be robust to alternative model parameter assumptions.. Use of tolterodine in patients with UI who discontinue initial therapy with generic oxybutynin lies within currently accepted benchmarks for cost-effectiveness.

Topics: Benzhydryl Compounds; Canada; Cost-Benefit Analysis; Cresols; Economics, Pharmaceutical; Humans; Mandelic Acids; Markov Chains; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence

We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Drug Prescriptions; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Parasympatholytics; Pharmaceutical Services; Phenylpropanolamine; Retrospective Studies; Time Factors; Tolterodine Tartrate; Urinary Incontinence

The effects of a new tachykinin NK(1) receptor antagonist, (aR, 9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione (TAK-637), on the micturition reflex were compared with those of drugs used for abnormally frequent micturition or incontinence. TAK-637 showed a characteristic effect on the distension-induced rhythmic bladder contractions in guinea pigs. The systemic administration of TAK-637 decreased the number but not the amplitude of the distension-induced rhythmic bladder contractions. A similar effect was observed in animals in which the spinal cord had been severed. TAK-637 also inhibited the micturition reflex induced by topical application of capsaicin onto the surface of bladder dome. From these results, it is concluded that TAK-637 inhibits sensory transmissions from the bladder evoked by both physiological and nociceptive stimuli by blocking tachykinin NK(1) receptors, possibly at the level of the spinal cord. On the other hand, the other drugs such as oxybutynin, tolterodine, propiverine, and inaperisone showed no effects on the frequency of the distension-induced rhythmic bladder contractions but decreased the contraction amplitude. Therefore, TAK-637 may represent a new class of drugs, which would be effective for abnormally frequent micturition without causing voiding difficulties due to decreased voiding pressure.

Topics: Animals; Benzhydryl Compounds; Benzilates; Capsaicin; Cholinergic Antagonists; Cresols; Dilatation; Dose-Response Relationship, Drug; Guinea Pigs; Male; Mandelic Acids; Muscarinic Antagonists; Muscle Contraction; Muscle Relaxants, Central; Naphthyridines; Parasympatholytics; Phenylpropanolamine; Piperidines; Propiophenones; Receptors, Tachykinin; Reflex; Tolterodine Tartrate; Urinary Bladder; Urination

TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.

Topics: Animals; Atropine; Benzhydryl Compounds; Benzilates; Carbachol; Cresols; Denervation; Dose-Response Relationship, Drug; Electric Stimulation; Guinea Pigs; Humans; In Vitro Techniques; Male; Mandelic Acids; Muscle Contraction; Naphthyridines; Pelvis; Phenylpropanolamine; Reflex; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Diseases

Topics: Aged; Behavior Therapy; Benzhydryl Compounds; Combined Modality Therapy; Cresols; Female; Humans; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Muscle Contraction; Parasympatholytics; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Male; Mandelic Acids; Phenylpropanolamine; Tartrates; Tolterodine Tartrate; Urinary Incontinence

Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of overactive bladder with symptoms of frequency, urgency and urge incontinence. We investigated the effects of tolterodine and its major active metabolite, DD 01 (PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in human isolated urinary bladder smooth muscles, using the muscle bath technique. Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome region of the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD 01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6) M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(-8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M) caused typical shifts to the right of the concentration-response curves for carbachol, except for higher concentrations (10(-5) M) of oxybutynin and propiverine, which caused a decrease of about 30% of the maximum contractile responses to carbachol. All the slopes of the regression lines of Schild plots were close to unity, and the rank order of pA2 values was: atropine = DD 01 = tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine. Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl-induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)-10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contraction of human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did not inhibit the residual contractions induced by electrical field stimulation at any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M) significantly inhibited the atropine-resistant part of the contractions. The results suggest that the inhibitory effects of tolterodine and DD 01 are mediated only by their antimuscarinic action, which is equal to that of oxybutynin

Topics: Aged; Benzhydryl Compounds; Benzilates; Calcium Chloride; Carbachol; Cresols; Dose-Response Relationship, Drug; Electric Stimulation; Female; Humans; In Vitro Techniques; Male; Mandelic Acids; Muscarinic Agonists; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Parasympatholytics; Phenylpropanolamine; Potassium Chloride; Tolterodine Tartrate; Urinary Bladder

Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms related to an overactive bladder. The aim of the present study was to compare the antimuscarinic properties of tolterodine with those of oxybutynin, in vitro and in vivo. Tolterodine effectively inhibited carbachol-induced contractions of isolated strips of urinary bladder from guinea pigs (K(B) 3.0 nM; pA2 8.6; Schild slope 0.97) and humans (K(B) 4.0 nM; pA2 8.4; Schild slope 1.04) in a concentration-dependent, competitive manner. The affinity of tolterodine was similar to that derived for oxybutynin (K(B) 4.4 nM; pA2 8.5; Schild slope 0.89) in the guinea-pig bladder. Tolterodine (21-2103 nmol/kg (0.01-1 mg/kg); intravenous infusion) was significantly more potent in inhibiting acetylcholine-induced urinary bladder contraction than electrically-induced salivation in the anaesthetised cat. In contrast, oxybutynin displayed the opposite tissue selectivity. Radioligand binding data showed that tolterodine bound with high affinity to muscarinic receptors in urinary bladder (K(i) 2.7 nM), heart (K(i) 1.6 nM), cerebral cortex (K(i) 0.75 nM) and parotid gland (K(i) 4.8 nM) from guinea pigs and in urinary bladder from humans (K(i) 3.3 nM). Tolterodine and oxybutynin were equipotent, except in the parotid gland, where oxybutynin bound with 8-times higher affinity (K(i) 0.62 nM). Binding data on human muscarinic m1-m5 receptors expressed in Chinese hamster ovary cells showed that oxybutynin, in contrast to tolterodine, exhibits selectivity (10-fold) for muscarinic m3 over m2 receptors. The K(B) value determined for oxybutynin (4.4 nM) in functional studies on guinea-pig bladder correlated better with the binding affinity at muscarinic M2/m2 receptors (K(i) 2.8 and 6.7 nM) than at muscarinic M3/m3 receptors (K(i) 0.62 and 0.67 nM). The tissue selectivity demonstrated for tolterodine in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. However, the combined in vitro and in vivo data on tolterodine and oxybutynin may indicate either that muscarinic M3/m3 receptors in glands are more sensitive to blockade than those in bladder smooth muscle, or that muscarinic M2/m2 receptors contribute to bladder contraction.

Topics: Adult; Aged; Analgesia; Animals; Atropine; Benzhydryl Compounds; Cats; CHO Cells; Cholinergic Antagonists; Cresols; Cricetinae; Dose-Response Relationship, Drug; Female; Guinea Pigs; Humans; Infusions, Intravenous; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Muscle Contraction; Phenylpropanolamine; Salivation; Tolterodine Tartrate; Urinary Bladder