Fesoterodine Research Articles

Risk of dementia associated with anticholinergic drugs for overactive bladder in adults aged ≥55 years: nested case-control study

ObjectiveTo investigate whether different anticholinergic drug treatments for overactive bladder have differential risks for incident dementia, in a large representative population of older adults in England.DesignNested case-control study.SettingGeneral practices in England providing data to the Clinical Practice Research Datalink (CPRD) GOLD database, with linked patient admission records from secondary care (Hospital Episode Statistics), 1 January 2006 and 16 February 2022Participants170 742 patients aged ≥55 years, with a first reported diagnosis of dementia during the study period, matched by age, sex, and general practice with 804 385 individuals without dementia (controls).InterventionsCumulative drug use (defined using total standardised daily dose) of different anticholinergic drugs used for the treatment of an overactive bladder, and a non-anticholinergic drug, mirabegron, in the period 3-16 years before a diagnosis of dementia (or equivalent date in matched controls).Main outcome measuresOdds ratios for onset of dementia associated with the different anticholinergic drugs used for the treatment of an overactive bladder, adjusted for sociodemographic characteristics, clinical comorbidities, and use of other anticholinergic drug treatments.ResultsThe study population comprised 62.6% women, and median age was 83 (interquartile range 77-87) years. 15 418 (9.0%) patients with dementia and 63 369 (7.9%) controls without dementia had used anticholinergic drugs for the treatment of an overactive bladder in the 3-16 years before diagnosis (or equivalent date for controls). The adjusted odds ratio for dementia associated with the use of any anticholinergic drug used to treat an overactive bladder was 1.18 (95% confidence interval (CI) 1.16 to 1.20), and was higher in men (1.22, 1.18 to 1.26) than women (1.16, 1.13 to 1.19). The risk of dementia was substantially increased with the use of oxybutynin hydrochloride (adjusted odds ratio 1.31, 95% CI 1.21 to 1.42 and 1.28, 1.15 to 1.43 for use of 366-1095 and >1095 total standardised daily doses, respectively), solifenacin succinate (1.18, 1.09 to 1.27 and 1.29, 1.19 to 1.39), and tolterodine tartrate (1.27, 1.19 to 1.37 and 1.25, 1.17 to 1.34). No significant increases in the risk of dementia associated with darifenacin, fesoterodine fumarate, flavoxate hydrochloride, propiverine hydrochloride, and trospium chloride were found. The association between mirabegron, a non-anticholinergic drug, and dementia was variable across the dose categories and might be caused by previous use of anticholinergic drugs for the treatment of an overactive bladder in these individuals.ConclusionsOf the different anticholinergic drugs used to treat an overactive bladder, oxybutynin hydrochloride, solifenacin succinate, and tolterodine tartrate were found to be most strongly associated with the risk of dementia in older adults. This finding emphasises the need for clinicians to take into account the possible long term risks and consequences of the available treatment options for an overactive bladder in older adults, and to consider prescribing alternative treatments that might be associated with a lower risk of dementia.

Disproportionality analysis of drug-induced dry mouth using data from the United States food and drug administration adverse event reporting system database

BackgroundDrug-induced dry mouth is an adverse reaction that can significantly affect the quality of life and mental state of patients. In this study, we aimed to identify the most common drugs associated with dry mouth using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. MethodsWe accessed data from the FAERS database between the first quarter of 2004 and the first quarter of 2024. The Medical Dictionary for Regulatory Activities was used to identify reports of dry mouth, and disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) were performed to examine the risk signals for dry mouth and its causative drugs. ResultsA total of 75,899 adverse event reports were related to dry mouth. Tiotropium bromide monohydrate (2080 cases) was associated with the majority of dry mouth cases. Disproportionality analysis revealed that the top five drugs with the highest reporting odds ratio (ROR) were darifenacin, solifenacin succinate, fesoterodine fumarate, tolterodine tartrate, and niraparib. Moreover, eight of the top 19 drugs that caused dry mouth were not identified as having major side effects in the package inserts. ConclusionTiotropium bromide monohydrate was the most frequently reported drug for dry mouth, whereas darifenacin had the highest ROR. Collectively, our findings emphasize the necessity for improved recognition and management of drug-induced dry mouth, particularly for medications not adequately flagged for this side effect in their labels.

Validated stability-indicating RP-HPLC assay method for fesoterodine fumarate in pharmaceutical products

The goal of the current study was to develop a precise, sensitive and validated reverse phase HPLC method for determination of fesoterodine fumarate (FST). The current investigation was performed for a stability indicating method in order to obtain both assay and impurity profiles of FST. All the experiment was done on HPLC Shimadzu Prominence 20A having stainless steel ACE5 C18 column with a particle size of 5µm and a dimension of 4.6 mm X 150 mm. The mobile phase was in gradient mode with mobile phase A (0.03M ammonium acetate buffer : acetonitrile : methanol (55:30:15 v/v) pH 3.8) and mobile phase B (water) . The flow rate was 1.2 mL/min and the wavelength 208 nm was selected for detection. This method was validated for linearity and range, accuracy, precision and robustness in accordance with ICH requirements. The retention time of fesoterodine was found as 11.0 min. The main degradation product 5-hydroxymethyltolterodine (5-HMT; active metabolite of FST) and the other process impurities; aldehyde, benzylated hydroxy, tolterodine ester, diester impurities were detected easily at the retention times 3.8, 13.5, 16.7, 21.5, 37.1 minutes, respectively. It was observed that the retention times of the main peak and its impurities were not affected and the selectivity of the method was proved under the applied stress conditions. With this developed method, FST and its impurities can easily be detected. It is also stable, simple, accurate, and completely validated RP-HPLC technique for the analysis of FST and related impurities that meets with ICH standards.

Online learning‐based predictive control of crystallization processes under batch‐to‐batch parametric drift

AbstractThis work considers a seeded fesoterodine fumarate (FF) cooling crystallization and presents the methodology and implementation of a real‐time machine learning modeling‐based predictive controller to handle batch‐to‐batch (B2B) parametric drift. Specifically, an autoencoder recurrent neural network‐based model predictive controller (AERNN‐MPC) is developed to optimize product yield, crystal size, and energy consumption while accounting for the physical constraints on cooling jacket temperature. Deviations in the kinetic parameters are considered in the closed‐loop simulations to account for the B2B parametric drift, and two error‐triggered online update mechanisms are proposed to address issues pertaining to the availability of real‐time crystal property measurements and are incorporated into the AERNN‐MPC to improve the model prediction accuracy. Closed‐loop simulation results demonstrate that the proposed AERNN‐MPC with online update, irrespective of the accessibility to real‐time crystal property data, achieves a desired closed‐loop performance in terms of maximizing product yield and minimizing energy consumption.

Predictive Control of Batch Crystallization Process Using Machine Learning

This work develops a framework for building machine learning models and machine learning-based predictive control schemes for batch crystallization processes. We consider a seeded fesoterodine fumarate cooling crystallization and dissolution in a batch reactor and present the methodology and implementation of simulation, modeling, and controller design. Specifically, to address the experimental data scarcity problem, we first develop a population balance model (PBM) based on published kinetic parameters to describe the formation of crystals via nucleation, growth, and agglomeration. Then, recurrent neural network (RNN) models are developed using data from extensive simulations of the semi-empirical PBM under various operating conditions to capture the process dynamic behavior. The model predictive control (MPC) scheme using RNN models is developed to optimize the crystallization process in terms of product yield, crystal size, and energy consumption, while accounting for the constraints on the manipulated inputs. Through open- and closed-loop simulations, it is demonstrated that the RNN models well capture the process dynamics, and the RNN-based MPC achieves desired product yield and crystal size with significantly improved computational efficiency.

Efficacy of fesoterodine fumarate (8 mg) in neurogenic detrusor overactivity due to spinal cord lesion or multiple sclerosis: A prospective study.

Antimuscarinic drugs are the first-line choice in the treatment of patients with neurogenic Detrusor Overactivity (nDO). Fesoterodine fumarate is the newest antimuscarinic drug. Limited data are published about the use of fesoterodine fumarate in patients suffering from neurogenic lower urinary tract dysfunction. Our study aims to determine the efficacy of fesoterodine fumarate on patients with nDO due to spinal cord lesion or multiple sclerosis (MS). This is an open-label prospective interventional study. Eligible patients were 18-80 years old with SCL or MS and nDO confirmed by a urodynamic study (UDS). At baseline, patients underwent a UDS to confirm nDO. Quality of life (QoL) was assessed by the Short-Form (SF) Qualiveen questionnaire. Patients received fesoterodine 8 mg/day for 3 months and were re-evaluated with UDS and SF-Qualiveen. The primary endpoint was the confirmation of the maximum detrusor pressure (Pdetmax ) reduction after treatment. Secondary endpoints were: evaluation of maximum bladder capacity and compliance and QoL effect. Statistical analysis included Wilcoxon-test using SPSSv26. One hundred and twenty-four patients completed the study. Ninety-five of them (76.6%) had SCL, while 29 (23.4%) had MS. Pdetmax , maximum bladder capacity, and compliance had significant reduction after treatment (p < .001) in the whole group and each subgroup. SF-Qualiveen revealed a significant increase in QoL in each group (p < .001). Fesoterodine fumarate (8 mg) is an efficacious drag in patients with SCL and MS, as it significantly decreases the detrusor pressure, increases the bladder capacity and compliance, and improves the QoL.

P0019 - Efficacy of fesoterodine fumarate in Neurogenic Detrusor Overactivity (NDO) due to Spinal Cord Lesion (SCL) or Multiple Sclerosis (MS) – A prospective study

P0019 - Efficacy of fesoterodine fumarate in Neurogenic Detrusor Overactivity (NDO) due to Spinal Cord Lesion (SCL) or Multiple Sclerosis (MS) – A prospective study

Stability-Indicating RP-HPLC Method for the Estimation of Process-Related Impurities and Degradation Products in Fesoterodine Fumarate by Using a Mass Spectrometric Compatible Mobile Phase.

The objective of the present work was to develop a sensitive, selective, accurate and precise stability-indicating HPLC method for quantification of degradation products and process-related impurities in fesoterodine fumarate extended-release tablets. The degradation profile was studied by conducting forced degradation studies and all the degradation products formed during degradation were separated. A chromatographic separation was achieved by using Waters Symmetry C18, 250 × 4.6mm, 5μm column, maintained at 30°C. Mobile phase A (0.05% trifluoroacetic acid in water) and mobile phase B (90% of 0.02% TFA in methanol and 10% of water) were used in gradient elution mode. A total of 75μL of each solution was injected and peak responses were quantified at 220nm. The method was found specific, precise, accurate, linear, rugged, robust and sensitive. During stability studies of fesoterodine fumarate extended-release tablets, one unknown impurity at relative retention time 1.37 was found increasing beyond the identification threshold. This impurity was isolated by using Preparative HPLC and structure was elucidated using mass and NMR spectroscopy. This method is a simple, inexpensive HPLC method that can be used as a routine quality control test for the estimation of impurities in fesoterodine fumarate extended-release tablets.

Crystal-size distribution-based dynamic process modelling, optimization, and scaling for seeded batch cooling crystallization of Active Pharmaceutical Ingredients (API)

Crystallization of active pharmaceutical ingredients (API) is one of the most important and complex multiphase engineering operations in pharmaceutical manufacturing industry. The desired physicochemical properties of solid crystalline product, such as crystal size distribution (CSD), are achieved by optimizing appropriate analyzed process operating conditions. In this application-derived study, an efficient straightforward mathematical modelling approach for the d value targeted CSD (characterized by 10th, 50th, and 90th centiles d10, d50, and d90) optimization of the API fesoterodine fumarate (FF) batches in different solvent mixtures on reactor dimension scales from 0.1 to 15 L is presented. The model is based on energy, mass, and population balance equations, the thermodynamic system equilibrium between solute/solution, and the kinetics of nucleation, crystal growth, and crystal agglomeration. In the first set of two experiments, the ability of the model to predict final CSD under chosen operating conditions was validated applying particular previously estimated kinetic parameters. An excellent statistical agreement between predicted and experimental CSD results was observed. Furthermore, the utility of the model to determine suitable operating conditions for the formation of FF crystals with d value defined CSD is presented. Two additional experiments were designed where stirring, cooling rate, and the amount of seed were optimally regressed. Good agreement between targeted and experimental CSD was shown and depending on the chosen vessel unit, mixing & cooling rates had the strongest relative impact on CSD. Algorithm may be beneficially utilized early during API industrial technological development, intensification, and scale-up, or transferred to continuous flow.

Process analytical technology-based (PAT) model simulations of a combined cooling, seeded and antisolvent crystallization of an active pharmaceutical ingredient (API)

Crystallization is one of the most important unit operations for production of active pharmaceutical ingredients (API) in pharmaceutical industry. This work studied the impact of solvent chemical composition on fesoterodine fumarate dissolution in 2-butanone/cyclohexane mixtures and seeded cooling crystallization, combining population balance equation (PBE) modelling with experiments. Thermodynamics, transport phenomena and kinetics of nucleation, crystal growth, agglomeration, and dissolution were taken into account, two in-line process analytical technologies (PAT) – attenuated total reflectance Fourier-transform infrared spectroscopy (ATR–FTIR) and focused beam reflectance measurement (FBRM) – were used for monitoring seeded experiments, and non-linear regression analysis was applied for parameter estimation. Cyclohexane not only decreased solute saturated solubility, but increased rates of all mechanisms. Model validation by temperature cycling showed a good agreement between results and simulations which opens up possibilities for further engineered optimization and control. Combined cooling & antisolvent crystallization (CCAC) experiment revealed a complex antisolvent impact on particle dynamics.

Randomized, controlled trial of fesoterodine fumarate for overactive bladder in Parkinson's disease.

To evaluate short-term efficacy and safety of fesoterodine fumarate in Parkinson's disease (PD) patients with overactive bladder (OAB) symptoms. This is a randomized, double-blind, placebo-controlled study. It also has an open-label extension phase. From May 2016 to May 2018, 63 patients were randomized to receive fesoterodine 4mg or placebo for 4weeks. At the end of 4weeks of randomization phase, patients were received fesoterodine fumarate 4mg daily for another 4 weeks at the open-label extension phase. The change in the mean number of micturition episodes per 24h period was the primary outcome measure of the study. The number of micturition episodes per 24h period significantly improved with the use of fesoterodine fumarate in the double-blind phase (p < 0.001). Also the mean number of nocturia and urgency episodes decreased in the fesoterodine group. In the open-label phase, the mean number of micturition, urgency and urgency urinary incontinence episodes were improved significantly. The number of nocturia episodes did not change in the open-label phase. Cognitive functions were stable after 4weeks of fesoterodine 4mg treatment. OAB symptoms were significantly improved in older adults with PD under fesoterodine fumarate treatment, and this advantage continued in the open-label portion in the short term. In this randomized controlled study, the cognitive functions of the participants were not affected by fesoterodine 4mg treatment compared with placebo.

Physicochemical properties and drug-release mechanisms of dual-release bilayer tablet containing mirabegron and fesoterodine fumarate.

Introduction: In this study, a dual release bi-layer tablet containing Fesoterodine fumarate (Fst) 5 mg and Mirabegron (Mrb) 50 mg was prepared to investigate the different release behavior of each drug in bilayer tablet. The bilayer tablet was prepared based on monolayer-tablet formulation of each drug.Methods: The optimized bi-layer tablet showed an in vitro dissolution profile similar to commercial reference tablets Toviaz and Betmiga, based on a satisfactory similarity factor. Drug-release kinetics of each drug in the bilayer tablet were evaluated based on dissolution profiles. Drug-release behavior was evaluated by observing the surface of each layer by scanning electron microscopy and measuring the changes in weight and volume of the tablet during dissolution. Drug transfer between each layer was also investigated by Fourier -transform infrared spectroscopic imaging by observing the cross-section of the bilayer tablet cut vertically during dissolution.Results: The release of Fst was well suited for the Higuchi model, and the release of Mrb was well suited for the Hixson-crowell model. Compared with dissolution rate of each monolayer tablet, that of Fst in the bilayer tablet was slightly reduced (5%), but the dissolution rate of Mrb in bilayer tablet was dramatically decreased (20%). Also, a drug-release study confirmed that polymer swelling was dominant in Fst layer compared with polymer erosion, and degradation was dominant in MRB layer. Fourier-transform infrared imaging and 3-D image reconstruction showed that drug transfer in the bilayer tablet correlates with the results of drug-release behavior.Conclusion: These findings are expected to provide scientific insights in the development of a dual-release bilayer drug-delivery system for Fst and Mrb.

Crystallization of fesoterodine fumarate active pharmaceutical ingredient: Modelling of thermodynamic equilibrium, nucleation, growth, agglomeration and dissolution kinetics and temperature cycling

The crystallization of active pharmaceutical ingredients (API) is an important, but complex unit operation in drug manufacturing industry, due to the diverse chemical nature of medicinal formulation compounds, several physicochemical phenomena that take place during particle formation process, and multi-phase governing resistances. This research paper presents a combined experimental–modelling approach to understanding fesoterodine fumarate crystallization and dissolution in 2-butanone. A rigorous in-house mechanistic model algorithm that includes calibration, thermodynamic equilibrium description, energy, mass and population balance equations, heat transfer limitations, and ordering, agglomeration and detachment step kinetics was developed. On the basis of experimentally-determined saturated solubility, a specified initial number of designed dissolution and cooling crystallization experiments was performed, monitored by attenuated total reflection Fourier-transform infrared (ATR–FTIR) spectroscopy, focused beam reflectance measurement (FBRM) technique and microscopy. The estimated kinetic parameters of transport, nucleation, crystal lattice growth, agglomeration and dissolution were evaluated by fitting the measured/simulated concentration curves with crystallite size distributions. Correlation was validated with additional trial results, observing a rather good agreement. The behaviour of the component during validations’ temperature cycling was thoroughly examined by simulations to achieve a solid final insight into mechanisms, which may aid further production development, optimization, as well as scale-up.

Detection of antimuscarinic agents tolterodine and fesoterodine and their metabolite 5-hydroxymethyl tolterodine by ion transfer voltammetry at a polarized room-temperature ionic liquid membrane

Ion transfer voltammetry at a polarized hydrophobic room temperature ionic liquid (RTIL) membrane was used for evaluation of the diffusion coefficients and the standard Gibbs energies of ion transfer of the protonated antimuscarinic agents tolterodine (TOL), fesoterodine (FES), and their common metabolite 5-hydroxymethyl tolterodine (5-HMT), as well as for their determination in the aqueous samples and urine. An analysis of the pH effect provided the parameters characterizing their lipophilicity both in their ionic and neutral forms confirming a remarkably low lipophilicity of 5-HMT. The application of the ion transfer voltammetry for a monitoring of the enzymatic hydrolysis of FES to 5-HMT was demonstrated. For determination of protonated TOL, FES, and 5-HMT in the aqueous samples, linear calibration dependences were plotted in the range 2.0–12.5 μmol L−1 with the mean limit of detection (LOD) 0.43 μmol L−1. Analogous linear calibration dependences were constructed for 10times diluted urine spiked with 2.0–12.5 μmol L−1 TOL, FES, and 5-HMT with the mean LOD 0.65 μmol L−1. Unfortunately, determination of 5-HMT in diluted urine samples was interfered by an unknown ionic urine component, which somewhat increased its particular LOD.

PD36-03 EARLY FESOTERODINE FUMARATE ADMINISTRATION PREVENTS THE ONSET OF NEUROGENIC DETRUSOR OVERACTIVITY AFTER SPINALIZATION IN RATS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II1 Apr 2018PD36-03 EARLY FESOTERODINE FUMARATE ADMINISTRATION PREVENTS THE ONSET OF NEUROGENIC DETRUSOR OVERACTIVITY AFTER SPINALIZATION IN RATS Mikolaj Przydacz, George Loutochin, Phillippe Cammisotto, Jakub Zimoch, Naciba Benlimame, Lysanne Campeau, and Jacques Corcos Mikolaj PrzydaczMikolaj Przydacz More articles by this author , George LoutochinGeorge Loutochin More articles by this author , Phillippe CammisottoPhillippe Cammisotto More articles by this author , Jakub ZimochJakub Zimoch More articles by this author , Naciba BenlimameNaciba Benlimame More articles by this author , Lysanne CampeauLysanne Campeau More articles by this author , and Jacques CorcosJacques Corcos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1726AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Onset of detrusor overactivity (DO) after spinal cord injury (SCI) affects patient′s quality of life and renal function. Electrical neuromodulation implemented immediately after injury in patients after SCI is currently the only recognized approach preventing DO. The aim of this experiment was to assess the urodynamic efficacy of early fesoterodine fumarate (FF) administration in preventing DO in a spinal cord transected (SCT) rat model and investigate whether observed effects were due to alternations in expression patterns of bladder muscarinic receptors. METHODS 33 Sprague-Dawley rats were allocated to 6 groups - Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10 and FF was continuously administered from post-op day 1. Cystometry was undertaken 6 weeks after SCT in awaked rats right before the animals were sacrificed. Changes of bladders layers were assessed by hematoxylin/eosin and Masson′s trichrome staining. Distribution of the receptors was investigated by immunofluorescence staining against muscarinic receptors (M1 to M5) and their prevalence was analyzed by Western blots. Comparisons were conducted using Kruskall-Wallis test (post-hoc Dunn test). RESULTS Urodynamic data: 6 weeks after SCT, intermicturition pressure was lower in low dose treated group (Group 4) compared to SCT controls (p<0.05) whereas maximum pressure was lower in most of the SCT treated rats (Groups 3-5) (p<0.01). Threshold pressure was lower in full time treated rats (Group 3-4) (p<0.05). Morphological data: No changes were noticed within the bladders layers in terms of degree of fibrosis and muscle hypertrophy. Expression of M2 receptors was lower in groups with wash-out period (Groups 5 and 6) (p<0.01) whereas expression of M3 receptors was higher in Groups 4 and 5 (p<0.01). CONCLUSIONS Early FF administration in a SCT rat model prevents the onset of DO and modifies profile of bladder muscarinic receptors. The treatment effect is sustained after a washout period. The evidence is strong enough to support clinical trials analyzing long-term prevention of DO in patients after SCI with the presented approach. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e727 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mikolaj Przydacz More articles by this author George Loutochin More articles by this author Phillippe Cammisotto More articles by this author Jakub Zimoch More articles by this author Naciba Benlimame More articles by this author Lysanne Campeau More articles by this author Jacques Corcos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

EXTRACTIVE-SPECTROPHOTOMETRIC DETERMINATION OF SOME ANTIMUSCARINIC ANTAGONIST IN TABLET FORMULATIONS USING ERIOCHROME CYANINE R

Objective: To develop and validate simple, rapid and sensitive spectrophotometric method for the assay of four antimuscarinic antagonists, namely oxybutynin (OXB), solifenacin (SOL), tolterodine (TOL) and fesoterodine (FES) in bulk and pharmaceutical formulations.Methods: The proposed method is based on the reaction of the selected drugs with eriochrome cyanine R (ECR) in buffered aqueous solution at pH 1.0. The formed ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 464 nm. All variables that affect on color intensity such as pH, buffer volume and concentration of ECR and extractive solvents were studied and optimized.Results: The calibration graphs were linear over the concentration range of 4–24, 4–32, 4–32 and 2–22 mg/ml for OXB, SOL, TOL and FES, respectively. The stoichiometry of the reaction was found to be 1:1 in all cases. Molar absorptivity values were found to be 2.043×104, 1.856×104, 1.798×104 and 2.856×104 l/mol/cm for OXB, SOL, TOL and FES, respectively. Excipients which used as an additive in commercial formulations did not interfere in the analysis.Conclusion: The developed method was successfully applied to determine OXB, SOL, TOL and FES in pharmaceutical preparations. The developed method can be used for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance.

586 - Early fesoterodine fumarate administration prevents the onset of neurogenic detrusor overactivity after spinalization in rats: Mechanism of action

586 - Early fesoterodine fumarate administration prevents the onset of neurogenic detrusor overactivity after spinalization in rats: Mechanism of action

Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model.

BackgroundIn spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.PurposeTo assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model.Methods33 Sprague-Dawley rats were allocated to 6 groups–Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn’s tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.ResultsPressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.ConclusionEarly administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea

Objectives: The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz) in Korean patients with overactive bladder (OAB) in routine clinical practice. Methods: This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator’s discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.Results: A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.Conclusion: These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

The short-term and long-term adverse ocular effects of fesoterodine fumarate

Aim: To evaluate the short-term and long-term effects of fesoterodine fumarate treatment which is used for overactive bladder (OAB) on pupil diameter (PD), intraocular pressure (IOP) and accommodation amplitude (AA).Method: Ophthalmic examination was performed before and after receiving medication (on the 30th and 90th day) on 120 eyes of 120 women whom were planned to begin anticholinergic treatment (fesoterodine fumarate, 4 mg/day, peroral) for OAB, prospectively. The changes in PD, IOP and AA were analyzed statistically.Results: The mean age of 120 women was 52.06 ± 9.39 years (30–70 years). The mean PD, IOP and AA values were 4.12 ± 0.61 mm (3.00–5.70 mm), 15.58 ± 1.74 mmHg (11–20 mmHg) 2.28 ± 1.26 Diopter (D) (0.50–5.50 D) at baseline; 4.68 ± 0.65 mm (3.20–5.80 mm), 16.11 ± 1.72 mmHg (11–20 mmHg), 1.68 ± 1.04 D (0.25–4.50 D) at 30th day; and 4.28 ± 0.58 mm (3.10–5.70 mm), 16.09 ± 1.96 mmHg (11–19 mmHg), 2.18 ± 1.19 D (0.50–5.00 D) at 90th day, respectively. Although increases in PD values and decreases in AA values were statistically significant (p < 0.001 for each), the changes in IOP values were not as such (p = 0.642). Visual complaint was not observed in any patient.Discussion: The newest anticholinergic medication in women with OAB increased the PD and decreased the AA statistically significantly. Clinically, it seems to be well-tolerated by the patient.