Overactive Bladder Research Articles

88 - Exploring the Effects of fMRI Scan Length on Brainstem Parcellations: Overactive Bladder Patients Versus Healthy Participants

88 - Exploring the Effects of fMRI Scan Length on Brainstem Parcellations: Overactive Bladder Patients Versus Healthy Participants

172 - Selective Bladder Denervation with Radiofrequency Ablation vs Intramuscular Botulinum Toxin Injection in Patients with Refractory Overactive Bladder: A Preliminary Report of Prospective Randomized Comparative Study

172 - Selective Bladder Denervation with Radiofrequency Ablation vs Intramuscular Botulinum Toxin Injection in Patients with Refractory Overactive Bladder: A Preliminary Report of Prospective Randomized Comparative Study

225 - Analysis of OABSS score improvement in overactive bladder patients during behavioral therapy while using the smart fun application 'USAPO'.

225 - Analysis of OABSS score improvement in overactive bladder patients during behavioral therapy while using the smart fun application 'USAPO'.

Reply to Editorial Comment on “External Validation Demonstrates Machine Learning Models Outperform Human Experts in Prediction of Objective and Patient-reported Overactive Bladder Treatment Outcomes”

Reply to Editorial Comment on “External Validation Demonstrates Machine Learning Models Outperform Human Experts in Prediction of Objective and Patient-reported Overactive Bladder Treatment Outcomes”

223 - An examination of the relationship between satisfaction with overactive bladder treatment and the doctor-patient gender: a questionnaire-based single institution study.

223 - An examination of the relationship between satisfaction with overactive bladder treatment and the doctor-patient gender: a questionnaire-based single institution study.

170 - Transcutaneous Posterior Tibial Nerve Stimulation on Demand During Multichannel Urodynamics: A New Approach in the Management of Overactive Bladder

170 - Transcutaneous Posterior Tibial Nerve Stimulation on Demand During Multichannel Urodynamics: A New Approach in the Management of Overactive Bladder

Associations of overactive bladder (OAB) with suicidal ideation incidence and all-cause mortality among the U.S. population

BackgroundFew studies have explored the correlation between overactive bladder (OAB) and suicidal ideation. This study aims to investigate the association between OAB and suicidal ideation, as well as the relationship between OAB and all-cause mortality among individuals with suicidal ideation.MethodsData from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed using cross-sectional and cohort study designs. Weighted multivariable logistic regression models were used to examine the association between OAB and suicidal ideation. Kaplan-Meier curves and weighted multivariable Cox proportional hazards models assessed the relationship between OAB and all-cause mortality among those with suicidal ideation. Interaction analyses on subgroups were conducted to validate the findings. Mediation analysis was performed to examine the effect of depression on the relationship between OAB and suicidal ideation.ResultsAmong 33,426 participants aged ≥ 20 years, 1,290 (3.8%) reported suicidal ideation. After adjusting for potential confounders, participants with OAB were 2.57 times more likely to have suicidal ideation (P < 0.001). Over an average follow-up of 87 months, 197 participants with suicidal ideation died. The Cox model revealed that participants with OAB had a 3.08 times higher risk of death (P = 0.006). Kaplan-Meier curves indicated higher survival rates for non-OAB participants. Mediation analysis indicates that depression significantly mediates the relationship between OAB and suicidal ideation, with a mediation proportion of 75.25% (P < 0.001).ConclusionsOAB is positively associated with the incidence of suicidal ideation and all-cause mortality among participants with suicidal ideation. Additionally, the association between OAB and suicidal ideation is mediated by depression.

Urodynamic study and its correlation with cardiac meta-iodobenzylguanidine (MIBG) in body-first and brain-first subtypes of Parkinson's disease.

Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of "body-first" and "brain-first" subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body-first and brain-first subtypes of PD using urodynamic studies (UDS). We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body-first or brain-first PD based on cardiac sympathetic denervation (CSD) using cardiac meta-iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body-first subtype). A total of 55 patients with PD were categorized into body-first PD (n = 37) and brain-first PD (n = 18) groups. The body-first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain-first PD group (p < 0.05 in both). Also, the body-first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain-first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume andnegatively correlated with OABSS and IPSS (p < 0.05 in all). Patients with the body-first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction.

Pelvic autonomic dysfunction is common in patients with pure autonomic failure.

Pure autonomic failure (PAF) presents primarily as cardiovascular autonomic failure and may phenoconvert to other neurodegenerative disorders. However, the involvement of other autonomic functions has been poorly evaluated. This study aims to characterize genitourinary and bowel dysfunction and explore their relationship with cardiovascular autonomic dysfunction. Pure autonomic failure patients underwent cardiovascular autonomic testing and an assessment of pelvic autonomic dysfunction using urinary, sexual symptoms questionnaires and a bladder diary. Demographic, clinical features and related medical comorbidities were assessed. Twenty-five patients (10 males) with PAF were included (mean age 71 ± 8 years; disease duration 13 ± 8 years). 96% (24/25) reported lower urinary tract symptoms, of which overactive bladder symptoms were most commonly reported (n = 23; 92%; median overactive subscore 8, interquartile range [IQR] 3-11), followed by voiding difficulties (n = 19; 76%; median low stream subscore 2, IQR 1-3) using the Urinary Symptom Profile; however, only four (16%) required clean intermittent self-catheterization. Sexual dysfunction was common (n = 21; 84%) using the Arizona Sexual Experience Scale. Mild faecal incontinence and constipation were reported. 86% (19/22) had nocturnal polyuria (NP) and the median NP index was 47% (IQR 38%-51%; normal range <33%). 77% (10/13) had voiding dysfunction and 31% (4/13) had post-void residual urine >100 mL. There were no significant correlations between the need for catheterization and the degree of NP with age, disease duration and cardiovascular autonomic parameters (p > 0.05). Nocturnal polyuria, genitourinary and bowel symptoms are commonly seen in PAF. The pathophysiology of NP in PAF is most likely multifactorial and may occur independent of cardiovascular autonomic failure.

Detection of Prescribing Cascades in Multimorbid Older Patients Hospitalized with Acute Unselected Illness

Abstract Background Prescribing cascades (PCs) occur when a new medication is prescribed to treat an unrecognized side-effect of another medication. PCs represent an important but often underrecognized aspect of inappropriate prescribing in older people with multimorbidity and associated polypharmacy and can result in avoidable morbidity and mortality. Numerous PCs are described in the literature, however, there are no prospective studies describing PC prevalence in older people. Therefore, we aimed to investigate the prevalence of PCs in acutely hospitalized older adults. Methods We undertook a prospective observational study, including adults ≥65years with polypharmacy (≥5 daily drugs) and multimorbidity (≥3 chronic disorders). Prescription medication lists were examined for the co-prescription of 31 drug pairs according to two pre-defined PC lists– ThinkCasades1 and of the explicit cascades published by Doherty et al2. PCs were defined as ‘definite’, ‘probable’, ‘possible’, ‘uncertain’ or ‘indeterminate’ according to specific criteria. Results We obtained prospective data on 300 patients (56% female, mean age 80.4yrs SD 7.2). 233 drug pairs were prescribed in the sequence of drug A → drug B, these occurred in 43% (n=130) of patients. Of the 233 pairs, 38% (n=88) were probable or possible PCs and 62% (n=145) were uncertain. 45 patients (15%) had ≥1 possible or probable PCs. The most commonly identified probable/possible PCs were diuretic → overactive bladder medication and calcium channel blocker → diuretic. Patients with an identified PC experienced higher mean levels of polypharmacy than patients with no PCs (11.7, SD 4.0 vs 9.6, SD 3.1, T= -4.97, p &amp;lt;0.001). Conclusion In this first-ever study to report prospective prevalence of PCs, possible or probable PCs were significantly prevalent among acutely hospitalized multimorbid older patients and were associated with higher levels of polypharmacy.McCarthy LM, et al. Drgs &amp; aging. 2022 Oct;39(10):829-40.Doherty AS, et al. Pharmacology research &amp; perspectives. 2022 Oct;10(5): e01008.

Urethral Bulking Agents for the Treatment of Urinary Incontinence: Efficacy, Safety, and Impact on the Overactive Bladder Symptoms with an Underlying Detrusor Overactivity.

Background: Mixed urinary incontinence (MUI) has always represented a major therapeutic challenge and the management of this type of incontinence is often complicated by uncertain outcomes. Surgical options include interventions targeting both stress urinary incontinence (SUI) and urge urinary incontinence (UUI), although there are no international published guidelines that dictate whether it is better to start with surgical management to address the SUI or UUI component after the failure of conservative treatment. The aim of the present study is to evaluate the effectiveness of the Macroplastique (MPQ) procedure on overactive bladder (OAB) symptoms in women with MUI with a minimum follow-up of 1 year. Methods: A retrospective analysis of prospectively collected data was performed in two tertiary reference centers. We enrolled all women complaining of symptoms of SUI and OAB, dry or wet, with a urodynamically confirmed diagnosis of MUI [urodynamic stress incontinence (USI) with detrusor overactivity (DO)], who took a previous ineffective antimuscarinic treatment and underwent the MPQ procedure. We considered as objectively cured women who did not leak urine during the stress test and with a 1 h pad-test negative, while International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), ICIQ-OAB, Patient Global Impression of Improvement (PGI-I) scale, and a Visual Analogue Scale (VAS) were used to assess subjective outcomes. Results: A total of forty-six patients who met the inclusion criteria and who underwent the MPQ procedure were considered for the analysis. At the 1-year mark of follow-up, 72% of patients were objectively cured at stress test and 65% were objectively cured at pad-test, while 72% of women declared themselves subjectively cured. OAB symptoms significantly improved after MPQ and a complete resolution of OAB was recorded in 35% of patients. Conclusions: This study demonstrated that MPQ is a safe and effective option for the treatment of female MUI. Furthermore, MPQ significantly improves the symptoms of OAB and is able to completely cure this condition in a relevant percentage of women with MUI when pharmacological treatment fails.

White Matter Magnetic Resonance Diffusion Measures in Multiple Sclerosis with Overactive Bladder.

Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS.

A historical perspective on anticholinergics in overactive bladder (OAB) treatment: “Foundations, current practices, and future prospects”

Antimuscarinics have long been the cornerstone of treatment for overactive bladder (OAB), with their use spanning decades. This paper reviews the pharmacological properties, historical use, clinical efficacy, and challenges associated with antimuscarinics, revealing that concerns regarding their side effects and lack of bladder selectivity have persisted throughout their history.While long-term efficacy and safety have been established in various populations, adherence remains low due to side effects such as dry mouth, constipation, and cognitive impairment. The risk of cognitive side effects has led to increased scrutiny in older adults, where polypharmacy and anticholinergic burden are significant concerns. Despite advances, including newer formulations like extended-release versions and transdermal applications that improve tolerability, the fundamental issues of adherence and side effects have not been fully resolved.Intravesical administration has been explored to reduce systemic side effects, though its use remains limited to specific patient populations. Future directions in OAB treatment focus on exploring new pharmacological targets, including ion channels, enzymatic pathways, and gene therapy, to develop more selective and effective therapies. Additionally, phenotyping patients with OAB and personalised medicine approaches may enhance treatment outcomes. Despite these persistent challenges, antimuscarinics remain a critical component in the management of OAB.

Recent developments in diagnostic ultrasound for lower urinary tract function.

Ultrasonography (US) is an essential tool in the clinical management of lower urinary tract dysfunction (LUTD), including lower urinary tract symptoms, overactive bladder, and benign prostatic hyperplasia, in which prostatic volume and post-void residual volume are routinely used to evaluate the pathophysiological characteristics of afflicted patients. US can also be employed to diagnose hydronephrosis and bladder calculus as complications of severe LUTD. Moreover, US is essential for identifying pathophysiological characteristics and surgical indications, predicting disease development and drug efficacy, and monitoring bladder function improvement by means of such parameters as bladder wall thickness, prostatic urethral length, intravesical prostatic protrusion, and prostatic urethral angulation/angle. Herein, I narratively review the recent advances in US approaches for the management of LUTD, especially in adult males.

Botulinum Neurotoxin Type A in paediatric non-neurogenic therapy resistant overactive bladder: a cohort study.

Intradetrusor Botulinum Neurotoxin Type A (BoNT-A) is an increasingly applied treatment modality for overactive bladder (OAB) in children with refractory urinary incontinence. Despite that, evidence is sparse, and the potential not fully understood. The aim of this study was to evaluate the effectiveness and safety of intradetrusor injection in children with refractory functional OAB and urinary incontinence. Furthermore, we aimed to identify predictors of efficacy and side effects to BoNT-A treatment. We conducted a cohort study of children with OAB and urinary incontinence who received intradetrusor injection of BoNT-A in the period 01.01.2016 to 31.12.2020 at our centre. All patients were refractory to standard urotherapy, anticholinergics, mirabegron and the combination of these treatments. Patients with neurogenic bladder were excluded. Primary endpoint was the reduction on the frequency of urinary incontinence episodes from baseline. Secondary endpoints included urodynamic parameters and uroflowmetry characteristics as well as side effects. Forty-three children (mean age at first treatment 10.7 ± 1.8, 30 males) were included. After first treatment, a reduction of ≥ 50% in incontinence episodes was seen in 58% of patients with daytime urinary incontinence (DUI) and 47% of patients with nocturnal enuresis (NE). Adverse events, mainly urinary tract infections (UTI), were reported by 16% of patients after first treatment. Our analysis identified normal cystometric compliance as a significant predictor of treatment effect We estimated the mean duration of effect to be approximately 7months. Intradetrusor BoNT-A injection appears to be a safe and effective option in treating refractory urinary incontinent children with overactive bladder. We identified cystometric compliance as a predictor of response. Most children necessitate repeated treatments. Further prospective and controlled studies are necessary in order to fully identify predictors and potential of treatment.

Investigation of Mirabegron-loaded Nanostructured Lipid Carriers for Improved Bioabsorption: Formulation, Statistical Optimization, andIn-VivoEvaluation.

Overactive bladder (OAB) is a usual medical syndrome that affects the bladder, and Mirabegron (MBG) is preferred medicine for its control. Currently, available marketed formulations (MYRBETRIQ® granules and MYRBETRIQ® ER tablets) suffer from low bioavailability (29-35%) hampering their therapeutic effectiveness and compromising patient compliance. By creating MBG nanostructured lipid carriers (MBG-NLCs) for improved systemic availability and drug release, specifically in oral administration of OAB treatment, this study aimed to address these issues. MBG-NLCs were fabricated using a hot-melt ultrasonication technique. MBG-GMS; MBG-oleic acid interaction was assessed by in silico molecular docking. QbD relied on the concentration of Span 80 (X1) and homogenizer speed (X2) as critical material attribute (CMA) and critical process parameter (CPP) respectively, while critical quality attributes (CQA) such as particle size (Y1) and cumulative drug release at 24h (Y2) were estimated as dependent variables. 32 factorial design was utilized to investigate the interconnection in variables that are dependent and independents. Optimized MBG-NLCs with a particle size of 194.4 ± 2.25nm were suitable for lymphatic uptake. A PDI score of 0.275 ± 0.02 and zeta potential of -36.2 ± 0.721mV indicated a uniform monodisperse system with stable dispersion properties. MBG-NLCs exhibited entrapment efficiency of 77.3 ± 1.17% and a sustained release in SIF of 94.75 ± 1.60% for 24h. MBG-NLCs exhibited the Higuchi model with diffusion as a release mechanism. A pharmacokinetic study in Wistar rats exhibited a 1.67-fold higher bioavailability as compared to MBG suspension. Hence, MBG-NLCs hold promise for treating OAB by improving MBG's oral bio absorption.

A Dataset for Constructing the Network Pharmacology of Overactive Bladder and Its Application to Reveal the Potential Therapeutic Targets of Rhynchophylline

Objectives: Network pharmacology is essential for understanding the multi-target and multi-pathway therapeutic mechanisms of traditional Chinese medicine. This study aims to evaluate the influence of database quality on target identification and to explore the therapeutic potential of rhynchophylline (Rhy) in treating overactive bladder (OAB). Methods: An OAB dataset was constructed through extensive literature screening. Using this dataset, we applied network pharmacology to predict potential targets for Rhy, which is known for its therapeutic effects but lacks a well-defined target profile. Predicted targets were validated through in vitro experiments, including DARTS and CETSA. Results: Our analysis identified Rhy as a potential modulator of the M3 receptor and TRPM8 channel in the treatment of OAB. Validation experiments confirmed the interaction between Rhy and these targets. Additionally, the GeneCards database predicted other targets that are not directly linked to OAB, corroborated by the literature. Conclusions: We established a more accurate and comprehensive dataset of OAB targets, enhancing the reliability of target identification for drug treatments. This study underscores the importance of database quality in network pharmacology and contributes to the potential therapeutic strategies for OAB.

An Improved and Efficient Practical Process for the Synthesis of Enantiomerically Pure Solifenacin Succinate as an Antimuscarinic Agent

Background: Solifenacin succinate is an active pharmaceutical drug molecule that is extremely effective in treating overactive bladder symptoms, such as urine incontinence, urgency, and frequent urination. The free base is yellow oil, and the salt solifenacin succinate forms yellowish crystals that are extremely stable and effective. Solifenacin is a very active antagonist due to its potent muscarinic M3 receptor antagonist characteristics. Furthermore, solifenacin is effective in the treatment of bowel syndrome (IBS) by blocking M3 receptors and a broad spectrum of bowel dysfunction. Objective: The objective of this study was to develop a practical and highly efficient scalable synthesis of enantiomerically pure solifenacin as an antimuscarinic agent. Methods: In this work, the Zn(OTf)2 catalyst was used to develop a novel, environmentally benign, high-yielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. Results: The synthesis of enantiomerically pure solifenacin succinate was achieved in seven steps using commercially available phenylethylamine and benzoyl chloride as the starting materials. We carried out the reaction optimization by treatment of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)- carbonyl chloride and (R)-(-)-3-Quinuclidinolin in the presence of Zn(OTf)2 catalyst. Furthermore, the solifenacin-free base was treated with succinic acid to afford its corresponding salt. The highlight of this protocol is the use of 20 mol% Zn(OTf)2 catalyst for the first time. The readily available starting materials, robustness, easy operation, high yield, and low cost make the approach more attractive and highly applicable. Conclusion: In summary, we developed a novel Zn(OTf)2-catalysed environmentally benign, highyielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. The proposed strategy is highly cost-effective and avoids the use of hazardous and unsafe sensitive, strong bases as well as tedious work-up procedures. Effective synthesis was achieved using readily available starting materials and reagents. Thus, the protocol is highly efficient, compatible, and commercially viable for the synthesis of important solifenacin products.

Trends of Overactive Bladder and Pharmacologic Treatment Among U.S. Women.

To evaluate and consider how prescribing practices have changed in relation to high-risk overactive bladder (OAB) medications. The objective of this study was to evaluate trends in the prevalence of OAB and pharmacologic treatment over time in the United States. Data from the National Health and Nutrition Examination Survey (NHANES, 2001-2018, n = 30,478) and the National Ambulatory Medical Care Survey (NAMCS, 2003-2019, n = 251,330) were used to identify women with symptomatic incontinence and overactive bladder (OAB) (NHANES) as well as determine the frequency of prescription use for OAB medications (NHANES and NAMCS) using sampling-based weights. Joinpoint regression was used to determine adjusted annual percent change (APC, adjusting for race, age, body mass index, and insurance status). Trends were assessed overall and by race, age, body mass index, and insurance status. The prevalence of OAB was 31.2% in the final survey year of NHANES (2017-2018). Women aged >65 years had the highest prevalence of OAB at 54% compared with other age groups. There was an overall increase in OAB (APC 1.24 [0.64, 1.84], P = 0.002) over time. Overall, only 3.5% of patients with symptoms of OAB reported pharmacologic treatment in NHANES. The NAMCS demonstrated a significant decrease in anticholinergic prescriptions from 2003 until 2019 (APC -6.44 [-9.77, -2.98], P = 0.001). However, in NHANES, there was no significant change in anticholinergic use (APC 0.62 [-20.2, 26.8], P = 0.944). There was a stable prevalence of β3-adrenergic agonist prescriptions since they were introduced to market (APC 0.65 [-2.24, 3.62], P = 0.616). This study demonstrates an increasing prevalence of OAB and highlights the likely undertreatment of symptomatic patients. The high and increasing prevalence coupled with the relative undertreatment of OAB underscores the importance of screening for this condition.

An Investigational Study on the Role of CYP2D6, CYP3A4 and UGTs Genetic Variation on Fesoterodine Pharmacokinetics in Young Healthy Volunteers.

Introduction: Fesoterodine is one of the most widely used antimuscarinic drugs to treat an overactive bladder. Fesoterodine is extensively hydrolyzed by esterases to 5-hydroxymethyl tolterodine (5-HMT), the major active metabolite. CYP2D6 and CYP3A4 mainly metabolize 5-HMT and are, therefore, the primary pharmacogenetic candidate biomarkers. Materials and Methods: This is a candidate gene study designed to investigate the effects of 120 polymorphisms in 33 genes (including the CYP, COMT, UGT, NAT2, and CES enzymes, ABC and SLC transporters, and 5-HT receptors) on fesoterodine pharmacokinetics and their safety in 39 healthy volunteers from three bioequivalence trials. Results: An association between 5-HMT exposure (dose/weight corrected area under the curve (AUC/DW) and dose/weight corrected maximum plasma concentration (Cmax/DW)), elimination (terminal half-life (T1/2) and the total drug clearance adjusted for bioavailability (Cl/F)), and CYP2D6 activity was observed. Poor/intermediate metabolizers (PMs/IMs) had higher 5-HMT AUC/DW (1.5-fold) and Cmax/DW (1.4-fold) values than the normal metabolizers (NMs); in addition, the normal metabolizers (NMs) had higher 5-HMT AUC/DW (1.7-fold) and Cmax/DW (1.3-fold) values than the ultrarapid metabolizers (UMs). Lower 5-HMT exposure and higher T1/2 were observed for the CYP3A4 IMs compared to the NMs, contrary to our expectations. Conclusions: CYP2D6 might have a more important role than CYP3A4 in fesoterodine pharmacokinetics, and its phenotype might be a better predictor of variation in its pharmacokinetics. An association was observed between different genetic variants of different genes of the UGT family and AUC, Cmax, and CL/F of 5-HMT, which should be confirmed in other studies.