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1.
Int J Nanomedicine ; 19: 8353-8371, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161357

RESUMEN

Introduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy. Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model. Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy. Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery.


Asunto(s)
Indoles , Lactobacillus , Microbiota , Polímeros , Vejiga Urinaria Hiperactiva , Vejiga Urinaria , Animales , Indoles/química , Indoles/farmacocinética , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Humanos , Polímeros/química , Microbiota/efectos de los fármacos , Ratas , Esferoides Celulares , Succinato de Solifenacina/farmacocinética , Succinato de Solifenacina/química , Succinato de Solifenacina/administración & dosificación , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Miocitos del Músculo Liso/efectos de los fármacos , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/administración & dosificación , Portadores de Fármacos/química
2.
Molecules ; 29(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38998963

RESUMEN

Solifenacin (SFC) is a potent muscarinic antagonist that effectively reduces bladder muscle contraction, thereby alleviating symptoms such as frequency of micturition and urgency. Oxidation of SFC leads to the formation of impurities like Impurity K. Effective analysis and control of this impurity is crucial for ensuring compliance with regulatory standards and safeguarding patient health. To address these challenges, we propose a novel one-step synthesis of Impurity K from SFC. Impurity K was synthesized using cerium(IV) ammonium nitrate (CAN) in water/acetonitrile as the solvent. Additionally, we describe a new HPLC-MS method for the detection of Impurity K in solifenacin succinate tablets.


Asunto(s)
Succinato de Solifenacina , Succinato de Solifenacina/química , Succinato de Solifenacina/análisis , Cromatografía Líquida de Alta Presión/métodos , Contaminación de Medicamentos , Espectrometría de Masas/métodos , Cerio/química , Antagonistas Muscarínicos/análisis , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/síntesis química , Comprimidos , Acetonitrilos/química , Cromatografía Líquida con Espectrometría de Masas
3.
Clin Neuropharmacol ; 47(4): 109-112, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008540

RESUMEN

OBJECTIVES: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative progressive disease of central nervous system that mostly affects young adults. (1) Because of involvement of spinal cord and brain, lower urinary dysfunction symptoms are commonly encountered. MS patients mostly show overactive bladder symptoms like urgency, frequent daytime urination, and urgency incontinence. Among MS patients, antimuscarinic therapy is the first-line treatment with overactive bladder symptoms as well as in general population yet 30% of the patients show insufficient improvement or intolerance to the treatment (2). In our study, our aim is to evaluate the efficacy and safety of mirabegron add-on treatment in MS patients after inadequate response to antimuscarinic monotherapy. METHODS: University of Kyrenia and Dr Burhan Nalbantoglu State hospital's databases were screened for the study. Seventy patients who were residents diagnosed with MS according to McDonald criteria were questioned. Among these patients, a total of 22 of them were included in the study. Inclusion criteria was at least 3 years of MS diagnosis, score of <6 at Expanded Disability Status Scale, and a score of ≥3 at Overactive Bladder Symptom Score Scale. RESULTS: Among selected patients, 10 mg solifenacin treatment was daily started and followed for 4 weeks. Mirabegron add-on treatment was initiated to the 11 patient who had inadequate improvement in overactive bladder symptom score. After mirabegron add-on treatment among 11 patient, there was a sufficient improvement in overactive bladder symptom score ( P < 0.008). CONCLUSIONS: In our study, we have found that antimuscarinic and mirabegron combination causes improved efficacy for overactive bladder in MS population.


Asunto(s)
Acetanilidas , Quimioterapia Combinada , Esclerosis Múltiple , Antagonistas Muscarínicos , Succinato de Solifenacina , Tiazoles , Vejiga Urinaria Hiperactiva , Humanos , Acetanilidas/uso terapéutico , Acetanilidas/efectos adversos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/etiología , Tiazoles/uso terapéutico , Tiazoles/efectos adversos , Succinato de Solifenacina/uso terapéutico , Proyectos Piloto , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Muscarínicos/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/complicaciones , Resultado del Tratamiento , Agentes Urológicos/uso terapéutico , Agentes Urológicos/efectos adversos
4.
BMC Urol ; 24(1): 97, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664686

RESUMEN

BACKGROUND: Overactive bladder is a common chronic urological disorder in children, liable to impact normal social activities, disrupt sleep and even impair self-esteem. We aimed to evaluate the efficacy and safety of solifenacin combined with biofeedback for paediatric overactive bladder. METHOD: Forty-five children with overactive bladder were enrolled and divided into three groups: 15 patients in Group A were treated with solifenacin, 15 cases in Group B with biofeedback, and the other 15 patients in Group C with the combination of solifenacin plus biofeedback. Each group was subdivided into the non-urge incontinence (non-UI) and urge incontinence (UI) groups. The remission rates were compared among the three groups at 2, 4, 8 and 12 weeks from the beginning of treatment. The side effects of solifenacin were recorded and followed up. RESULT: After 2 weeks since initial treatment, the complete response rates were 33.3% (5/15), 20.0% (3/15), and 53.3% (8/15) in the three groups. At 4 weeks, the complete remission rates were 46.7% (7/15), 33.3% (5/15), and 60.0% (9/15) respectively. Moreover, the complete remission rates of the UI groups were higher than the non-UI groups (p < 0.05). At 8 weeks, the complete response rates were 53.3% (8/15), 40.0% (6/15), and 67.7% (10/15). At 12 weeks, the complete response rates were 67.8% (10/15), 60.0% (9/15), and 86.7% (13/15). The complete response rates were higher and urodynamic parameters were improved obviously in group C than the other two groups (p < 0.05) during the follow-ups. The median voiding frequency decreased and median functional bladder capacity increased obviously in Group C after 4 weeks (p < 0.05). Dry mouth was observed in 2 patients (4.4%). 2 patients experienced constipation (4.4%), and neither case was severe. The symptoms of these four patients had relieved by reducing the dose of solifenacin. CONCLUSION: Solifenacin combined with biofeedback had good efficacy and compliance for children experiencing overactive bladder. It took only 2 weeks to achieve the complete response rate over 50%, especially for the improvement of UI symptoms.


Asunto(s)
Biorretroalimentación Psicológica , Succinato de Solifenacina , Vejiga Urinaria Hiperactiva , Humanos , Succinato de Solifenacina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/terapia , Niño , Femenino , Masculino , Resultado del Tratamiento , Terapia Combinada , Antagonistas Muscarínicos/uso terapéutico , Adolescente , Preescolar
5.
Sci Rep ; 14(1): 7499, 2024 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553529

RESUMEN

Persistence is important for the success in the treatment of women with overactive bladder syndrome (OAB). We aimed to identify the predictors of non-persistence in women with OAB after first-line medical treatment. All consecutive women with OAB (n = 608), who underwent urodynamic studies and received first-line medical treatment (5 mg of solifenacin or 25 mg of mirabegron per day) in a referral medical center, were reviewed. Mirabegron (hazard ratio [HR] = 0.711) was associated with a higher persistence rate, compared to solifenacin. Mirabegron treatment (HR = 0.269) was less likely to switch medication; however, a high Urogenital Distress Inventory score (HR = 1.082) was more likely to switch medication. Furthermore, old age (HR = 1.050, especially for ≥ 75 years) and high voided volume (dL, HR = 1.420, especially for voided volume ≥ 250 ml) were associated with added medication at follow-up. Additionally, women with low parity (HR = 0.653, especially for parity ≤ 3) and a low Incontinence Impact Questionnaire (IIQ-7) score (HR = 0.828, especially for IIQ-7 score ≤ 7) were associated with improvement without medication. In conclusion, mirabegron can be considered as the first frontline treatment to increase the persistence rate and decrease the rate of switched medications, compared to solifenacin. In addition, combination therapy or higher-dose monotherapy could be used as the first front-line treatment for women ≥ 75 years of age or with ≥ 250 ml of voided volume.


Asunto(s)
Tiazoles , Vejiga Urinaria Hiperactiva , Incontinencia Urinaria , Humanos , Femenino , Anciano , Succinato de Solifenacina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Resultado del Tratamiento , Acetanilidas/uso terapéutico , Incontinencia Urinaria/tratamiento farmacológico , Incontinencia Urinaria/complicaciones , Antagonistas Muscarínicos/uso terapéutico
6.
Urogynecology (Phila) ; 30(3): 214-222, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38484234

RESUMEN

IMPORTANCE: There is strong evidence for long-term cognitive effects with anticholinergic use. Differences in insurance coverage of anticholinergics and beta-3 agonists hinder individualization of overactive bladder (OAB) treatment. OBJECTIVES: The aims of the study were to assess individual and family health insurance plan coverage for select OAB medications and to compare coverage of preferred medications to those with a greater risk of cognitive dysfunction. STUDY DESIGN: This cross-sectional study analyzed formularies for the top 7 U.S. medical insurers. Coverage tiers were assessed for the following 7 OAB medications: (1) oxybutynin instant-release 5 mg, (2) oxybutynin extended-release 5 mg, (3) solifenacin 5 mg, (4) trospium instant-release 20 mg, (5) trospium extended-release 60 mg, (6) mirabegron 25 mg, and (7) vibegron 75 mg. Coverage was compared between nonpreferred (oxybutynin, solifenacin) and preferred medications (trospium, mirabegron, vibegron). Coverage scores, representing a weighted average based on coverage tier frequency relative to the number of plans investigated for each state or insurer, were generated with a lower coverage score indicating better coverage (range, 0.2-1.0). RESULTS: A total of 2,780 insurance plans from 41 states representing a 47% market share for the individual and family marketplace were evaluated. Oxybutynin IR had the best coverage score across insurers (0.2) while vibegron had the worst (0.92). Preferred medications were more often designated to higher tiers with worse coverage compared with nonpreferred medications (P < 0.001). Less concordance in coverage between insurers was noted for anticholinergics with greater bladder specificity and for extended-release formulations. CONCLUSIONS: Despite risks with anticholinergics, beta-3 agonists were more expensive across all insurers highlighting the need for expanded coverage of preferred medications to avoid cognitive dysfunction when undergoing treatment for OAB.


Asunto(s)
Acetanilidas , Ácidos Mandélicos , Tiazoles , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Succinato de Solifenacina/uso terapéutico , Estudios Transversales , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico
7.
Adv Ther ; 41(4): 1652-1671, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38430402

RESUMEN

INTRODUCTION: This study aimed to assess overactive bladder (OAB) treatment patterns and factors associated with effectiveness and persistence. METHODS: A prospective, longitudinal, observational registry study of adults starting OAB therapy with mirabegron or antimuscarinics was undertaken. Primary endpoints were time from treatment initiation to discontinuation/switching; proportion who discontinued/switched; and reasons for discontinuation/switching. Secondary endpoints included OAB Symptom Score (OABSS), OAB Questionnaire: Short Form, and OAB Bladder Assessment Tool scores; factors associated with effectiveness and persistence; and safety. RESULTS: In total, 556 patients initiating mirabegron and 250 initiating antimuscarinics were enrolled. There was no treatment switch, change, or discontinuation in 68.5% of the mirabegron initiator group and median time to treatment change was not reached. Mean initial treatment duration was 130.8 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, and patients with mild and moderate OAB had significantly better persistence with mirabegron than those with severe OAB. Urinary tract infection was the most common adverse event with mirabegron. There was no treatment switch, change, or discontinuation in 60.4% of the antimuscarinics initiator group and median time to treatment change was not reached. Solifenacin was the most frequent initial treatment (66.0%). Mean treatment duration was 122.2 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, while patients with OAB medication in the 12 months before enrollment had significantly better persistence with antimuscarinics than those with no previous OAB medication. Dry mouth was the most common adverse event with antimuscarinics. CONCLUSIONS: Mirabegron and solifenacin were commonly prescribed as first-line OAB medications. There was no treatment switch, change, or discontinuation in more than 60% of the mirabegron initiator and antimuscarinics initiator groups. Mean initial treatment duration was 130.8 days and 122.2 days for mirabegron and antimuscarinics, respectively. Graphical Abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov NCT03572231.


Asunto(s)
Tiazoles , Vejiga Urinaria Hiperactiva , Agentes Urológicos , Adulto , Humanos , Acetanilidas/efectos adversos , Antagonistas Muscarínicos/efectos adversos , Estudios Prospectivos , Sistema de Registros , República de Corea , Succinato de Solifenacina/uso terapéutico , Taiwán , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/efectos adversos
8.
Prostate Cancer Prostatic Dis ; 27(2): 305-311, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38553627

RESUMEN

BACKGROUND: Low-intensity shockwave therapy (Li-SWT) can improve bladder function through enhancement of angiogenesis and nerve regeneration and suppression of inflammation and overactivity. In this trial, we aimed to evaluate the efficacy of Li-SWT on persistent storage symptoms after transurethral surgery (TUS) for benign prostatic obstruction (BPO). METHODS: Between July 2020 and July 2022, 137 patients with persistent storage symptoms; urgency episodes/24 h ≥ 1 and daytime frequency ≥8, for at least three months after TUS for BPO were randomly allocated to Li-SWT versus sham versus solifenacin 10 mg/day in 3:1:1 ratio. The primary end point was the percent reduction from baseline in overactive bladder symptom score (OABSS) at 3-month follow-up. The changes in 3-day voiding diary parameters, quality of life (QoL) score, peak flow rate and residual urine at 3 and 6-month follow-up were compared. Treatment-related adverse effects were also evaluated. RESULTS: Baseline data were comparable between groups. The percent reduction from baseline in OABSS at 3-month follow-up was significantly higher in Li-SWT compared to sham (-55% versus -11%), and it was comparable between Li-SWT and solifenacin-10 (-55% versus -60%). Li-SWT achieved significant improvement like solifenacin-10 in 3-day voiding diary parameters and QoL score at 3-month follow-up. This improvement remained comparable between Li-SWT and solifenacin-10 at 6-month follow-up. No adverse effects related to Li-SWT were noted apart from tolerable pain during the procedure. Solifenacin-10 was associated with bothersome adverse effects in 73% of the patients with 11.5% discontinuation rate. CONCLUSIONS: Li-SWT ameliorates persistent storage symptoms and promotes QoL after TUS for BPO, with comparable efficacy and better tolerance compared to solifenacin.


Asunto(s)
Hiperplasia Prostática , Calidad de Vida , Resección Transuretral de la Próstata , Humanos , Masculino , Anciano , Resección Transuretral de la Próstata/métodos , Resección Transuretral de la Próstata/efectos adversos , Hiperplasia Prostática/terapia , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Persona de Mediana Edad , Succinato de Solifenacina/administración & dosificación , Succinato de Solifenacina/uso terapéutico , Resultado del Tratamiento , Estudios de Seguimiento , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/etiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Método Doble Ciego
9.
J Urol ; 211(1): 26-36, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37871329

RESUMEN

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.


Asunto(s)
Succinato de Solifenacina , Vejiga Urinaria Hiperactiva , Niño , Humanos , Suplementos Dietéticos , Antagonistas Muscarínicos , Calidad de Vida , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vitamina D/uso terapéutico
10.
J Chem Neuroanat ; 136: 102375, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38123002

RESUMEN

Demyelinating diseases are a type of neurological disorder characterized by the damage to the myelin sheath in the central nervous system. Promoting the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) is crucial for treatment. Non-selective muscarinic receptor (MR) antagonists have been shown to improve remyelination in rodent models, although the mechanisms are still unclear. In this study, we treated cuprizone (CPZ)-induced demyelination mouse model with different concentrations of Solifenacin (Sol), a selective M3 receptor antagonist, to determine the optimal concentration for promoting remyelination. Behavioral tests and Luxol fast blue (LFB) staining were used to observe the extent of remyelination, while immunofluorescence was used to measure the expression levels of myelin-related proteins, including myelin basic protein (MBP) and platelet-derived growth factor receptor alpha (PDGFR-α). Western blot analysis was employed to analyze the expression levels of molecules associated with the Wnt/ß-catenin signaling pathway. The results showed that Sol treatment significantly promoted myelin regeneration and OPCs differentiation in CPZ-induced demyelination mouse model. Additionally, Sol treatment inhibited the Wnt/ß-catenin signaling pathway and reversed the effects of CPZ on OPCs differentiation. In conclusion, Sol may promote the differentiation of OPCs by inhibiting the Wnt/ß-catenin signaling pathway, making it a potential therapeutic option for central nervous system demyelinating diseases.


Asunto(s)
Enfermedades Desmielinizantes , Remielinización , Ratones , Animales , Cuprizona/toxicidad , Succinato de Solifenacina/efectos adversos , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/metabolismo , Vía de Señalización Wnt , Oligodendroglía , Diferenciación Celular , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
11.
Wiad Lek ; 76(11): 2401-2405, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38112356

RESUMEN

OBJECTIVE: The aim: To improve the results of treatment of hyperactive bladder syndrome in men of working age on the background of barotrauma and stress, as a consequence of combat trauma. PATIENTS AND METHODS: Materials and methods: An analysis of the questionnaire and the results of the clinical examination of 32 patients, injured servicemen and people who were injured in combat zones was carried out. The drug solifenacin succinate was used in the treatment complex, which is a specific antagonist of M3 subtype cholinergic receptors. Its influence allows you to achieve relaxation of the bladder detrusor and reduce the contractility of hyperactive bladder. RESULTS: Results: The main criterion for the effectiveness of the treatment was a decrease in the number of urgent cases, the frequency of urination and manifestations of nocturia by 50% or more, which was considered a positive effect. At the same time, the positive effect was differentiated as follows : an improvement of these parameters by 75% or more from the initial value which is a good result; reduction of symptoms in the range of 50-75% is satisfactory; less than 50% is an unsatisfactory result. A positive effect from the treatment after 8 weeks was observed in 88% of patients, of which 52% had a good result and 36% had a satisfactory result. CONCLUSION: Conclusions: The proposed complex of treatment of hyperactive bladder syndrome as a result of combat trauma against the background of barotrauma with neurological consequences and chronic stress allows to achieve a pronounced clinical effect in the vast majority of male patients of working age. And the diagnostic complex allows you to emphasize aspects of clinical vigilance, both for doctors of a specialized branch and of doctors of a general direction.


Asunto(s)
Barotrauma , Vejiga Urinaria Hiperactiva , Humanos , Masculino , Vejiga Urinaria , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/etiología , Succinato de Solifenacina/uso terapéutico , Succinato de Solifenacina/farmacología , Barotrauma/complicaciones , Barotrauma/inducido químicamente , Barotrauma/tratamiento farmacológico
14.
Braz. J. Pharm. Sci. (Online) ; 58: e20849, 2022. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1403763

RESUMEN

Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate


Asunto(s)
Animales , Ratas , Metaboloma/efectos de los fármacos , Metabolómica/métodos , Succinato de Solifenacina/farmacología , Metabolismo/efectos de los fármacos , Ratas Wistar
15.
urol. colomb. (Bogotá. En línea) ; 30(4): 277-285, 15/12/2021. tab, ilus
Artículo en Español | LILACS, COLNAL | ID: biblio-1369044

RESUMEN

Objetivo Evaluar la costoefectividad incremental del régimen combinado de mirabegron/solifenacina en comparación con el uso temprano de toxina botulínica, desde la perspectiva del sistema de salud colombiano, para el tratamiento de adultos con vejiga hiperactiva. Métodos Se empleó un modelo de Markov en que se comparan dos secuencias de tratamiento, una con y otra sin mirabegron/solifenacina, para evaluar la costoefectividad en un horizonte temporal de cinco años. Debido a la perspectiva de análisis, sólo se tuvieron en cuenta los costos médicos directos. La eficacia del tratamiento evaluado y su comparador fue medida en términos de la reducción de episodios diarios de incontinencia y de la frecuencia de micciones. Los costos fueron expresados en pesos colombianos de 2019, y se aplicó una tasa de descuento de 5% tanto para desenlaces como para costos. Resultados Para el caso base, el costo del tratamiento en la secuencia que incluye mirabegron/solifenacina fue mayor, pero generó un mayor número de años de vida ajustados por calidad, y así e obtuvo una razón de costoefectividad incremental de $13.637,184 si se considera el desenlace de reducción de episodios diarios de incontinencia de 50%, y de $29.313,848 si se considera el del 100%. Conclusiones De acuerdo con los resultados de esta evaluación, para un horizonte de análisis de cinco años, la secuencia de tratamiento con mirabegron/solifenacina es una alternativa costoefectiva, si se considera un umbral de disposición a pagar de tres veces el producto interno bruto (PIB) per cápita.


Aim To evaluate the incremental cost-effectiveness of the combined regimen of mirabegron/solifenacin compared with the early use of botulinum toxin, from the perspective of the Colombian health system, for the treatment of adults with overactive bladder. Methods A Markov model comparing two treatment sequences, one with and one without mirabegron/solifenacin, was used to assess cost-effectiveness over a five-year period. Due to the perspective of the analysis, only direct medical costs were considered. The efficacy of the evaluated treatment and its comparator was measured in terms of the reduction in the daily incontinence episodes and the frequency of micturition. The costs were expressed in Colombian pesos of 2019, and a discount rate of 5% was applied for both outcomes and costs. Results For the base case, the cost of the treatment in the sequence that includes mirabegron/solifenacin was higher, but it generated a greater number of quality-adjusted years of life, thus obtaining an incremental cost-effectiveness ratio of $13,637,184 when considering the outcome of 50% of reduction in the daily incontinence episodes, and $29,313,848 when considering 100%. Conclusions According to the results of the present assessment, for a five-year period of analysi, the mirabegron/solifenacin treatment sequence is a cost-effective alternative when considering a threshold of willingness to pay three times the per capita gross domestic product (GDP).


Asunto(s)
Humanos , Síndrome , Vejiga Urinaria Hiperactiva , Guanosina Difosfato , Efectividad , Toxinas Botulínicas , Resultado del Tratamiento , Succinato de Solifenacina , Identidad de Género
16.
Int. braz. j. urol ; 47(3): 596-609, May-June 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1154501

RESUMEN

ABSTRACT Background: Many medical therapies have been tested to deal with urinary stent-related symptoms (USRS). Several preventive and pharmaceutical methods have been already used for better compatibility of stents. However, the existing evidence for pharmacological treatment is still controversial. This study aims to evaluate the effects of pregabalin, solifenacin, and combination therapy on ureteral double-J stent-related symptoms following ureteroscopy and transureteral lithotripsy (TUL). Materials and methods: In a randomized controlled clinical trial, from November 2017 to March 2019, 256 patients who underwent ureteroscopy were enrolled. Patients were randomly divided into four groups including: group A received pregabalin 75mg BID (twice daily), group B received solifenacin 5mg orally once daily, group C received combination of pregabalin and solifenacin and the group D (control) given no drugs. Results: One hundred and fifty-one (58.9%) males and 101 (41.1%) females were enrolled in this study with a mean age of 43.47±7 (p=0.32, p=0.67). USSQ domains score such as urinary symptoms, pain, general condition, work performance, sexual matters and additional problems were significantly differenced during second and fourth week of follow-up among study groups (p <0.0001). In Tukey's multiple comparison test, urinary symptoms (p=0.735), pain (p=0.954) and sexual matters (p=0.080) in second week and work performance in forth week in group B was not significantly better than group D. Only group C in all indexes of USSQ showed significantly beneficial effects over group D (p <0.0001). Conclusion: Combination therapy of pregabalin and solifenacin has a significant effect on stent-related symptoms and is preferred over monotherapy of the respected medications.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Uréter , Stents/efectos adversos , Succinato de Solifenacina/uso terapéutico , Calidad de Vida , Pregabalina/uso terapéutico , Persona de Mediana Edad
17.
Int. braz. j. urol ; 47(1): 73-81, Jan.-Feb. 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1134307

RESUMEN

ABSTRACT Introduction: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. Objectives: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. Patients and Methods: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. Results: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Conclusion: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.


Asunto(s)
Humanos , Preescolar , Niño , Adolescente , Enuresis , Enuresis Nocturna/tratamiento farmacológico , Antagonistas Colinérgicos , Desamino Arginina Vasopresina/uso terapéutico , Tartrato de Tolterodina , Succinato de Solifenacina
18.
Int. braz. j. urol ; 46(2): 185-193, Mar.-Apr. 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1090573

RESUMEN

ABSTRACT Objective To evaluate the effects of solifenacin, darifenacin, and propiverine on nasal-, subfoveal-, temporal choroidal thicknesses (NCT, SFCT, TCT), intraocular pressure (IOP) and pupil diameter (PD). Materials and Methods Patients with overactive bladder (OAB) diagnosed according to The International Continence Society were administered with solifenacin, darifenacin or propiverine on a daily basis between November 2017 and May 2018. NCT, SFCT, TCT, IOP, and PD of these patients were measured and compared as initial, fourth and twelfth weeks. Results A total of 165 patients (330 eyes) with OAB were evaluated. Solifenacin (n=140) significantly reduced IOP from 17.30±2.72 mmHg to 16.67±2.56 mmHg (p=0.006) and 16.57±2.41 mmHg (p=0.002), at the fourth and twelfth weeks, respectively. Darifenacin (n=110) significantly reduced NCT from 258.70±23.96 μm to 257.51±22.66 μm (p=0.002) and 255.36±19.69 μm (p=0.038), at the fourth and twelfth weeks, respectively. Propiverine (n=80) significantly increased PD from 4.04±0.48 mm to 4.08±0.44 mm (p=0.009) and 4.09±0.45 mm (p=0.001), at the fourth and twelfth weeks, respectively. Conclusion These findings can help to decide appropriate anticholinergic drug choice in OAB patients. We finally suggest further well-designed randomized prospective studies with a larger population to evaluate the anticholinergic-related complications in eyes.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Pirrolidinas/efectos adversos , Bencilatos/efectos adversos , Benzofuranos/efectos adversos , Pupila/efectos de los fármacos , Coroides/efectos de los fármacos , Antagonistas Muscarínicos/efectos adversos , Succinato de Solifenacina/efectos adversos , Presión Intraocular/efectos de los fármacos , Pirrolidinas/administración & dosificación , Bencilatos/administración & dosificación , Benzofuranos/administración & dosificación , Estudios Prospectivos , Estudios de Seguimiento , Antagonistas Muscarínicos/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Succinato de Solifenacina/administración & dosificación , Persona de Mediana Edad
19.
Int. braz. j. urol ; 46(4): 575-584, 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1134201

RESUMEN

ABSTRACT Objective and Hypothesis We aimed to investigate the reasons of storage symptoms ( SS) after transurethral resection of the prostate (TURP). The hypothesis was that a positive correlation would be identified between preoperative and postoperative SS in patients with undergoing TURP and starting early solifenacin treatment in patients with high preoperative SS would be reasonable. In addition, we aimed to analyze multiple other risk factors for post-TURP SS. Materials and Methods A total of 160 patients undergoing TURP were prospectively evaluated and divided into two groups according to their OABS. Those with a score of ≥10 points were Group 1 (G1), and those with <10 points Group 2 (G2). In addition, patients in each group were randomly further divided into two subgroups: those who were started on 5 mg solifenacin succinate in the early postoperative period (G1/G2 A) and those who were not (G1/G2 B). In additions to SS Preop, perop and at the 3rd-month of postoperatively 14 variable were evaluated. The effects of these factors, surgery and the efficacy of an early medical treatment on the postoperative SS were investigated. LUTS were assessed by International Prostate Symptom Score (IPSS) and SS were assessed by sum of IPSS 2, 4 and 7 questionnaires (Storage, S- IPSS). Results Preoperative IPSS and S-IPSS were significantly higher in G1 (p<0.001); there was a significant improvement at IPSS, S-IPSS, QoL score, Qmax, and PVR for all groups after surgery. Only preoperative S-IPSS was found to have significant effect on postoperative SS (p<0.001). There was a significant difference between G1A and G1B but no significant difference between G2A and G2B in terms of SS at postoperatively. In addition to this, prostatic volume was found smaller than non-symptomatic patients in de novo SS patients. Conclusion TURP provides significant improvement in both storage and voiding symptoms. The predictive value of the preoperative S-IPSS on postop SS is significant. These results suggest that 5 mg solifenacin succinate treatment in the early postoperative period may be beneficial for patients with high preoperative SS and may not be beneficial in others. Small prostatic volume may bode ill for postoperative SS in the patients with de novo SS.


Asunto(s)
Humanos , Masculino , Anciano , Resección Transuretral de la Próstata , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/tratamiento farmacológico , Factores de Riesgo , Resultado del Tratamiento , Succinato de Solifenacina/uso terapéutico , Persona de Mediana Edad
20.
Int. braz. j. urol ; 45(4): 782-789, July-Aug. 2019. tab
Artículo en Inglés | LILACS | ID: biblio-1019895

RESUMEN

ABSTRACT Purpose To evaluate the efficacy and tolerability of mirabegron in females with overactive bladder (OAB) symptoms after surgical treatment for stress urinary incontinence (SUI). Materials and Methods The study was conducted with a prospective, randomized and double-blinded design. 62 patients over the age of 40 who met the inclusion-exclusion criterias of the study were enrolled and randomly divided into two groups as Group A (mirabegron 50mg) and B (solifenacin 5mg). Patients were compared based on efficacy of treatment [Patient Perception of Bladder Condition (PPBC) scale and micturition diaries], safety of treatment (heart rate, systolic and diastolic blood pressure, adverse events), number of micturitions per day, patient's satisfaction status after treatment [Visual Analog Scale(VAS)] and quality of life. Results The mean age of the population was 48.2±3.8 years and the duration of OAB symptoms was 5.9±2.9 months. Baseline values for the mean number of micturitions, volume voided in each micturition, nocturia episodes, urgency and urgency incontinence episodes were 15.3±0.34, 128±3.88mL, 3.96±1.67, 5.72±1.35 and 4.22±0.69, respectively. After treatment, values for these parameters were 11.7±0.29, 164.7±2.9mL, 2.25±0.6, 3.38±0.71, 2.31±0.49 respectively. Quality of life score, symptom bother score, VAS for treatment satisfaction score, PPBC score after treatment were 66.1±0.85, 43.7±0.77, 4.78±0.14, 4.78±0.14, respectively. There were no significant differences between two groups on any parameter. However, mirabegron showed better tolerability than solifenacin, particularly after 6 months. Conclusion Mirabegron is safe, effective and tolerable in the long-term treatment of females with OAB symptoms after surgery for stress urinary incontinence.


Asunto(s)
Humanos , Femenino , Adulto , Tiazoles/uso terapéutico , Incontinencia Urinaria de Esfuerzo/cirugía , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agonistas de Receptores Adrenérgicos beta 3/uso terapéutico , Acetanilidas/uso terapéutico , Calidad de Vida , Valores de Referencia , Incontinencia Urinaria de Esfuerzo/fisiopatología , Método Doble Ciego , Estudios Prospectivos , Reproducibilidad de los Resultados , Resultado del Tratamiento , Antagonistas Muscarínicos/uso terapéutico , Vejiga Urinaria Hiperactiva/fisiopatología , Escala Visual Analógica , Succinato de Solifenacina/uso terapéutico , Persona de Mediana Edad
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