RESUMO
Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94â¯cm H2O⯱ 26.12 standard deviation (SD) to 21.07â¯cm H2O⯱ 17.32 SD (Pâ¯< 0.001, nâ¯= 34). Maximum bladder pressure (MBC) increased by 34% from 260.45â¯ml⯱ 200.26 SD to 348.45â¯ml⯱ 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.
Assuntos
Ácidos Mandélicos , Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Humanos , Administração Intravesical , Alemanha , Ácidos Mandélicos/uso terapêutico , Ácidos Mandélicos/administração & dosagem , Ácidos Mandélicos/efeitos adversos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Antagonistas Muscarínicos/efeitos adversos , Resultado do Tratamento , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Agentes Urológicos/administração & dosagem , Agentes Urológicos/efeitos adversosRESUMO
BACKGROUND: Many factors contribute to developing and conducting a successful multi-data source, non-interventional, post-authorization safety study (NI-PASS) for submission to multiple health authorities. Such studies are often large undertakings; evaluating and sharing lessons learned can provide useful insights to others considering similar studies. OBJECTIVES: We discuss challenges and key methodological and organizational factors that led to the delivery of a successful post-marketing requirement (PMR)/PASS program investigating the risk of cardiovascular and cancer events among users of mirabegron, an oral medication for the treatment of overactive bladder. RESULTS: We provide context and share learnings, including sections on research program collaboration, scientific transparency, organizational approach, mitigation of uncertainty around potential delays, validity of study outcomes, selection of data sources and optimizing patient numbers, choice of comparator groups and enhancing precision of estimates of associations, potential confounding and generalizability of study findings, and interpretation of results. CONCLUSIONS: This large PMR/PASS program was a long-term commitment from all parties and benefited from an effective coordinating center and extensive scientific interactions across research partners, scientific advisory board, study sponsor, and health authorities, and delivered useful learnings related to the design and organization of multi-data source NI-PASS.
Assuntos
Acetanilidas , Vigilância de Produtos Comercializados , Tiazóis , Bexiga Urinária Hiperativa , Humanos , Tiazóis/efeitos adversos , Tiazóis/administração & dosagem , Vigilância de Produtos Comercializados/métodos , Bexiga Urinária Hiperativa/tratamento farmacológico , Acetanilidas/efeitos adversos , Acetanilidas/administração & dosagem , Acetanilidas/uso terapêutico , Farmacoepidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Projetos de Pesquisa , Agentes Urológicos/efeitos adversos , Agentes Urológicos/administração & dosagem , Fonte de InformaçãoRESUMO
Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy. Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE. Design, Setting, and Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021. Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25). Main Outcomes and Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities. Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76). Conclusions and Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Fragilidade/diagnóstico , Hiperplasia Prostática/tratamento farmacológico , Índice de Gravidade de Doença , Agentes Urológicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Doxazossina/administração & dosagem , Doxazossina/efeitos adversos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Finasterida/administração & dosagem , Finasterida/efeitos adversos , Seguimentos , Idoso Fragilizado , Fragilidade/complicações , Avaliação Geriátrica , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Agentes Urológicos/administração & dosagemRESUMO
BACKGROUND: The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control. METHODS: In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule'an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis. RESULTS: The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively. CONCLUSIONS: These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.
Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Animais , China , Modelos Animais de Doenças , Finasterida/administração & dosagem , Masculino , Folhas de Planta , Próstata/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Agentes Urológicos/administração & dosagemRESUMO
Mirabegron (MYRBETRIQ®), a beta-3 adrenergic agonist developed by Astellas Pharma Inc., is well established as a treatment for overactive bladder in adults and is available as extended-release (ER) tablets administered once daily. More recently, mirabegron has been investigated in pediatric patients with neurogenic detrusor overactivity (NDO) and received its first approval in this indication in pediatric patients aged ≥â¯3 years on 25 March 2021 in the USA. In addition to mirabegron ER tablets (which can be used in pediatric patients weighing ≥â¯35 kg), mirabegron is available as an ER oral suspension (MYRBETRIQ® Granules) for pediatric patients; in those weighing <â¯35 kg, only the ER oral suspension formulation should be used. The ER tablet and ER oral suspension formulations are not substitutable on a mg-by-mg basis. This article summarizes the milestones in the development of mirabegron for NDO leading to this pediatric first approval.
Assuntos
Acetanilidas/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Aprovação de Drogas/métodos , Tiazóis/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Administração Oral , Adolescente , Criança , Pré-Escolar , Ensaios Clínicos Fase III como Assunto/métodos , Feminino , Humanos , Masculino , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnósticoRESUMO
OBJECTIVE: To characterize the timing and effectiveness of medical management in resolving stent-dependent ureteral compression secondary to idiopathic retroperitoneal fibrosis (RPF), the long-term relevant outcomes, and the side effects of treatment. METHODS: A retrospective review of RPF patients diagnosed from 2002-2018 was performed. Patients with hydronephrosis due to ureteral involvement that were managed with medication and with temporary stenting as needed, but without initial ureterolysis, were included. Patient demographics and RPF management details were obtained, including the following subsequent events: ureterolysis, nephrectomy, recurrent upper tract obstruction, and medication side effects. RESULTS: Fifty-two patients met inclusion criteria. Resolution of ureteral obstruction with medical management and temporary renal drainage as needed occurred in 36 (69%) patients with a median stent duration of 16 months, and median clinical and radiographic follow up of 4.2 and 3.3 years, respectively. Recurrent obstruction after a stent-free period occurred in 9 (18%) patients. Ureterolysis was performed in 8 (15%) patients at a median of 2.2 years for medication intolerance, lack of radiographic response to medication, or persisting pain. Potential medication side effects occurred in 6 (12%) patients. CONCLUSIONS: Medical management supported successful resolution of ureteral obstruction in 69% of patients without the need for ureterolysis after temporary renal drainage using stents, with rare incidence of worsening renal dysfunction or medication side effect. To date, this is the largest reported series of systematically managed RPF patients with obstructive uropathy receiving initial medical therapy and serves to counsel patients and advise urologists and nephrologists of the expected course and advantages and disadvantages of medical versus surgical management.
Assuntos
Hidronefrose/terapia , Fibrose Retroperitoneal/complicações , Stents , Obstrução Ureteral/terapia , Agentes Urológicos/administração & dosagem , Adulto , Terapia Combinada , Drenagem/instrumentação , Feminino , Seguimentos , Humanos , Hidronefrose/epidemiologia , Hidronefrose/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Fibrose Retroperitoneal/terapia , Estudos Retrospectivos , Resultado do Tratamento , Ureter/efeitos dos fármacos , Ureter/cirurgia , Obstrução Ureteral/epidemiologia , Obstrução Ureteral/etiologia , Agentes Urológicos/efeitos adversosRESUMO
The selective ß 3-adrenoceptor agonist mirabegron, an established alternative to antimuscarinic therapy for patients with overactive bladder, induces additional effects against receptors, transporters, and hepatic enzymes. The present study aimed to elucidate the effects of mirabegron on muscarinic receptors in the rat bladder using radioligand binding and functional assays. Mirabegron (0.1-100 µM) inhibited specific [N-methyl-3H]scopolamine methyl chloride binding in the bladder and other tissues of rats in a concentration-dependent manner. Binding affinity in the bladder was similar to that in the heart and significantly higher than those in the submaxillary gland and brain. Mirabegron induced the concentration-dependent relaxation of carbachol-induced contractions in the rat isolated bladder. Further analyses using a two-site model revealed that the relative quantities of high- and low-affinity components for mirabegron were 44.5% and 55.5%, respectively. Respective pEC50 values were 7.06 and 4.97. Based on the receptor binding affinity and pharmacokinetics of mirabegron, muscarinic receptor occupancy in the human bladder for 24 hours after the administration of a single oral dose of 50 mg mirabegron was 37%-76%. The present results demonstrate for the first time that mirabegron may relax the detrusor smooth muscle not only by ß 3-adrenoceptor activation but also muscarinic receptor blockade. SIGNIFICANCE STATEMENT: Mirabegron, the first selective ß 3-adrenoceptor agonist, represents an alternative to antimuscarinic agents for management of overactive bladder (OAB). The present study aimed to clarify whether mirabegron directly binds to muscarinic receptors and affects cholinergic agonist-induced contractions in rat urinary bladder and to predict muscarinic receptor occupancy in human bladder after oral administration of mirabegron. The results demonstrated that mirabegron therapy for patients with OAB may be due not only to ß 3-adrenoceptor activation but also muscarinic receptor blockade.
Assuntos
Acetanilidas/farmacocinética , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Antagonistas Muscarínicos/farmacocinética , Tiazóis/farmacocinética , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/farmacocinética , Acetanilidas/administração & dosagem , Acetanilidas/uso terapêutico , Administração Oral , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Animais , Encéfalo/metabolismo , Masculino , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Contração Muscular , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Glândula Submandibular/metabolismo , Tiazóis/administração & dosagem , Tiazóis/uso terapêutico , Bexiga Urinária/metabolismo , Agentes Urológicos/administração & dosagem , Agentes Urológicos/uso terapêuticoRESUMO
PURPOSE OF REVIEW: To analyze the literature on current conservative treatment options for Peyronie's disease (PD). RECENT FINDINGS: Conservative therapy with intralesional collagenase clostridium histolyticum (CCH) is safe and efficacious in either the acute or chronic phases of PD. Combination treatment with penile traction therapy (PTT) can produce even better results. While most PTT devices require extended periods of therapy up to 8 h per day, the RestoreX® device can be effective at 30-90 min per day. A variety of conservative therapies are available for treatment of PD. The available literature does not reveal any treatment benefit of oral therapies. Intralesional therapy is the mainstay conservative treatment of PD. Intralesional CCH therapy is the first Food and Drug Administration-approved intralesional therapy and represents the authors' preference for medical therapy. The most effective conservative management of PD likely requires a combination of therapies.
Assuntos
Tratamento Conservador , Colagenase Microbiana/administração & dosagem , Induração Peniana/terapia , Agentes Urológicos/administração & dosagem , Doença Aguda , Doença Crônica , Terapia Combinada , Tratamento Conservador/métodos , Humanos , Injeções Intralesionais , Masculino , Colagenase Microbiana/uso terapêutico , Induração Peniana/tratamento farmacológico , Induração Peniana/cirurgia , Tração/métodos , Agentes Urológicos/uso terapêuticoRESUMO
PURPOSE OF REVIEW: To highlight and review encouraging preliminary studies behind several alternative products and interventions for erectile dysfunction (ED). RECENT FINDINGS: Alternative treatments for ED are becoming more prevalent with increased consumer interest. "Natural" products are sold online, and numerous clinics offer various off-label and investigational interventions. These alternative treatments have demonstrated varying degrees of efficacy in randomized trials and meta-analyses, but none of these interventions has robust enough evidence to be considered first-line therapy. These treatments may find a role in combination with guideline treatments or may be used in novel penile rehabilitation research protocols. With growing interest in alternative treatment for men's health, an awareness of the literature is imperative for patient counsel. Alternative treatments, like L-arginine, have a growing body of evidence for efficacy in combination with PDE5i, and low-intensity shock wave therapy and stem cell therapy continue to demonstrate encouraging outcomes in ED trials.
Assuntos
Terapias Complementares , Disfunção Erétil/terapia , Alprostadil/administração & dosagem , Aminoácidos/uso terapêutico , Terapias Complementares/métodos , Tratamento por Ondas de Choque Extracorpóreas , Humanos , Oxigenoterapia Hiperbárica , Masculino , Saúde do Homem/tendências , Pênis , Fitoterapia , Plasma Rico em Plaquetas , Transplante de Células-Tronco , Ondas Ultrassônicas , Agentes Urológicos/administração & dosagem , Vibração/uso terapêuticoRESUMO
PURPOSE OF REVIEW: To review the current literature on acute management of traumatic penile fracture, with a specific discussion of those injuries following collagenase clostridium histolyticum (CCH) injections for the treatment of Peyronie's disease. RECENT FINDINGS: The immediate repair of traumatic penile fracture injury is associated with significantly better prognosis for long-term sexual health. Corporal disruption following CCH administration has several distinct features, and the trend is to manage these patients conservatively in the absence of urethral injury. Traumatic penile fracture repair continues to have excellent results when performed immediately following injury. The post-CCH treatment setting portends increased difficulty during surgical management and can be successfully managed in most cases by conservative measures.
Assuntos
Colagenase Microbiana/administração & dosagem , Induração Peniana/tratamento farmacológico , Pênis/lesões , Agentes Urológicos/administração & dosagem , Tratamento Conservador , Humanos , Injeções Intralesionais , Masculino , Colagenase Microbiana/uso terapêutico , Doenças do Pênis/tratamento farmacológico , Doenças do Pênis/cirurgia , Doenças do Pênis/terapia , Induração Peniana/complicações , Pênis/cirurgia , Ruptura/cirurgia , Resultado do Tratamento , Agentes Urológicos/uso terapêuticoRESUMO
This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Disfunção Erétil/diagnóstico por imagem , Sintomas do Trato Urinário Inferior/diagnóstico por imagem , Próstata/diagnóstico por imagem , Hiperplasia Prostática/patologia , Tecido Adiposo/patologia , Progressão da Doença , Quimioterapia Combinada , Disfunção Erétil/etiologia , Disfunção Erétil/patologia , Finasterida/administração & dosagem , Finasterida/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/tratamento farmacológico , Estudos Retrospectivos , Tansulosina/administração & dosagem , Tansulosina/uso terapêutico , Agentes Urológicos/administração & dosagem , Agentes Urológicos/uso terapêuticoRESUMO
OBJECTIVES: To investigate the long-term efficacy, quality of life (QoL), and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese patients with nocturia. METHODS: A long-term, multicenter phase 3 study was conducted that enrolled Japanese male and female patients with nocturia (NCT03051009). Male patients received desmopressin 25- or 50-µg ODTs, and female patients received desmopressin 25-µg ODTs for up to 1 year. The primary endpoint was safety. Secondary endpoints included change from baseline in number of nocturnal voids, time to first awakening to void, and QoL assessments (nocturia-specific zQoL [N-QoL], Insomnia Severity Index [ISI], and Hsu bother score). RESULTS: Overall, 503 patients were enrolled. Reductions from baseline in mean number of nocturnal voids were observed in all treatment groups from week 1 (-0.62 to -1.00), with improvements continuing through week 52 (-1.39 to -1.71). Changes from baseline above or approximating a clinically meaningful improvement were seen by week 52 in the disease-specific N-QoL total score (improved by 11.5-22.6), ISI (improved by -3.9 to -7.1), and Hsu bother scores (improved by -1.5 to -2.0). Adverse events (AEs) were reported in 54.9% of desmopressin-treated patients. Most AEs were mild or moderate in severity. CONCLUSIONS: Desmopressin ODTs (25 and 50 µg) demonstrated long-term efficacy, improved QoL, and were well tolerated in Japanese male and female patients with nocturia treated for up to 1 year. Clinically meaningful improvements in patients' QoL, assessed by N-QoL, sleep quality, and bother, occur later than objective symptom improvements, such as voids.
Assuntos
Desamino Arginina Vasopressina/uso terapêutico , Noctúria/tratamento farmacológico , Qualidade de Vida , Agentes Urológicos/uso terapêutico , Desamino Arginina Vasopressina/administração & dosagem , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Noctúria/psicologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Agentes Urológicos/administração & dosagemRESUMO
To investigate the reliability of newly defined CT-related parameters and cardiovascular risk factors in groups adjusted for stone size and location to predict spontaneous stone passage (SP) of uncomplicated ureteral stones ≤ 10 mm. The data of 280 adult patients with solitary unilateral ureteral stones ≤ 10 mm in diameter in non-contrast computed tomography were prospectively recorded. All patients undergoing a four-week observation protocol with medical expulsive therapy using tamsulosin were divided into two groups according to SP or no SP. Demographic, clinical and radiological findings of these groups were recorded. Spontaneous stone passage was observed in 176 (62.9%) of the patients, whereas the SP rate was 57.6% for 118 upper ureteral stones and 66.7% for 162 lower ureteral stones. The SP rate was 13.3 times greater with ureteral wall thickness < 1.88 mm, 4.4 times greater with a ratio of ureter to stone diameter of < 1.24, 3.4 times greater with Framingham score of < 11.5%, 2 times greater with neutrophil lymphocyte ratio < 1.96, 1.9 times greater with ureteral diameter < 6.33 mm and 1.5 times greater with stone volume < 38.54 mm3. Lower levels of ureteral wall thickness, ratio of ureter to stone diameter, Framingham score, neutrophil lymphocyte ratio, ureteral diameter, stone volume and absence of hydronephrosis were found to be more successful predictors. We consider that the success rate can be increased by selection of the proper option (observation or active treatment) according to these predictors.
Assuntos
Tansulosina/administração & dosagem , Tomografia Computadorizada por Raios X , Ureter/diagnóstico por imagem , Cálculos Ureterais/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Adulto , Feminino , Seguimentos , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento , Cálculos Ureterais/diagnósticoRESUMO
The aim of this investigation was to characterize and compare the pharmacokinetics (PK) of the antimuscarinic drug solifenacin in pediatric patients with overactive bladder (OAB) or neurogenic detrusor overactivity (NDO) utilizing data from three phase III trials. LION was a placebo-controlled, 12-week trial in children (5-<12 years) and adolescents (12-<18 years) with OAB. MONKEY and MARMOSET were open-label, 52-week trials in children and adolescents or younger children (6 months-<5 years), respectively, with NDO. During the trials, solifenacin doses could be titrated to weight-adjusted pediatric equivalent doses (PEDs) of 2.5, 5, 7.5, or 10 mg day-1 . Nonlinear mixed effects modeling was used to develop population PK models to characterize the PK in patients with either OAB or NDO. Overall, 194 children and adolescents received solifenacin. At the time of PK sampling, the majority (119/164 [72.6%] patients) were receiving PED10 once daily. All population models included first-order oral absorption, a lag time, and interindividual variability. PK analysis showed that apparent clearance was similar in both patient populations. Mean apparent oral plasma clearance (CL/F), apparent volume of distribution during the terminal phase (Vz /F), and terminal half-life (t1/2 ) were higher in adolescents than in children, but median time to maximum plasma concentration (tmax ) was similar. Dose-normalized exposure results were similar for both younger and older patients with OAB or NDO. In conclusion, population PK modeling was used to successfully characterize solifenacin PK in pediatric patients with OAB or NDO. Similar solifenacin PK characteristics were observed in both populations.
Assuntos
Antagonistas Muscarínicos/farmacocinética , Succinato de Solifenacina/farmacocinética , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/metabolismo , Agentes Urológicos/farmacocinética , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Antagonistas Muscarínicos/administração & dosagem , Método Simples-Cego , Succinato de Solifenacina/administração & dosagem , Bexiga Urinária Hiperativa/diagnóstico , Agentes Urológicos/administração & dosagemRESUMO
PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Administração Intravesical , Animais , Toxinas Botulínicas Tipo A/administração & dosagem , Citocinas/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Ratos , Ratos Sprague-Dawley , Bexiga Urinária Hiperativa/metabolismo , Agentes Urológicos/administração & dosagem , Urotélio/metabolismoRESUMO
AIMS: Local anesthesia protocols for intradetrusor onabotulinum toxin A (BoNTA) injection lack standardization. We aimed to determine if an alkalinized lidocaine solution is more effective than lidocaine only. METHODS: Patients of both genders aged 18 or above enlisted for intradetrusor BoNTA injection (idiopathic, neurogenic, and bladder pain syndrome) were included in a double-blinded randomized controlled trial after obtaining their informed consent. All participants filled a bladder diary and a urine culture was performed. Subjects were randomized 1:1 to Protocol A (20 ml 2% lidocaine + 10 ml 8.4% sodium bicarbonate) or Protocol B (20 ml 2% lidocaine + 10 ml 0.9% saline solution). A Numeric Rating Scale (0-10) was used to assess the level of pain immediately after the procedure (primary endpoint). Secondary endpoints included pain after 1 h, urinary tract infection, acute urinary retention, and hematuria related to the procedure. RESULTS: A total of 116 patients were randomized. Baseline characteristics (age, sex, indication, and bladder diary parameters) of patients in Group A and B were similar. Pain scores at the end of the procedure were significantly lower with the alkalinized solution (Protocol A and B, respectively, 2.37 ± 0.31 vs. 4.44 ± 0.36, p < .01). No differences were observed 1 h after treatment (Protocol A and B, respectively, 0.54 ± 0.17 vs. 0.69 ± 0.19, p = .487). The only adverse event reported was mild-to-moderate self-limited hematuria in 15.4% of patients. CONCLUSIONS: The use of an alkalinized lidocaine solution has proven to be significantly superior to lidocaine only as local anesthesia before intradetrusor BoNTA injection, suggesting that this may be considered a first-line option.
Assuntos
Anestésicos Locais/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Lidocaína/administração & dosagem , Dor/tratamento farmacológico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da DorRESUMO
OBJECTIVE: To determine the patient-perceived effectiveness and tolerability of mirabegron compared to solifenacin in a multiple sclerosis (MS) population with overactive bladder (OAB) symptoms. MATERIALS AND METHODS: MS patients with OAB symptoms who were not on medication for their urinary symptoms at enrollment were prospectively recruited. Patients enrolled in years 1-2 were prescribed mirabegron, whereas patients enrolled in years 3-4 were prescribed solifenacin. At enrollment and 6-week follow-up, patients completed several patient reported outcome measures. The primary outcome was change in OAB Questionnaire Short Form (OAB-q SF) symptom severity and minimal clinically important difference (MCID) achievement. The Patient Assessment of Constipation Symptoms (PAC-SYM) was used to assess bowel function over the treatment period. RESULTS: Sixty-one patients were enrolled. The majority of the mirabegron (70%) and the solifenacin (69%) group achieved the OAB-q SF symptom severity MCID. The solifenacin group had a statistically significant greater decrease in its end of study OAB-q SF score (Δ = -37.87 vs -20.43, P = .02). Constipation improved in the mirabegron group and worsened in the solifenacin group (ΔPAC-SYM = -0.38 vs +0.22; P = .02), with 30% of patients prescribed solifenacin experiencing worsening above the MCID threshold. CONCLUSION: Among MS patients, we demonstrated similar response rates to mirabegron and solifenacin, with approximately 50%-70% achieving each patient reported outcome measure's MCID. Though this small study showed some short-term evidence that improvement in urinary symptom severity was greater with solifenacin, this potential benefit must be weighed against the observed risk of worsening constipation. Further studies are needed to confirm these findings.
Assuntos
Acetanilidas/administração & dosagem , Esclerose Múltipla/complicações , Succinato de Solifenacina/administração & dosagem , Tiazóis/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Acetanilidas/efeitos adversos , Adulto , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Índice de Gravidade de Doença , Succinato de Solifenacina/efeitos adversos , Tiazóis/efeitos adversos , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/etiologia , Agentes Urológicos/administração & dosagem , Agentes Urológicos/efeitos adversosRESUMO
Alfuzosin is a medication approved by the US Food and Drug Administration to treat benign prostatic hyperplasia symptoms. Bioequivalence studies are demanded by regulatory authorities to evaluate the expected in vivo biological similarity of 2 formulations of a medication. The aim of this study is to assess the bioavailability of the generic (test) and branded (reference) formulations of 10-mg alfuzosin extended-release tablets after oral administration to healthy adults under fed conditions. The study used a comparative randomized, single-dose, 2-way crossover open-label study design. Thirty-three participants were recruited and completed the clinical assessment. The pharmacokinetic parameters maximum plasma concentration (Cmax ), area under the plasma concentration-time curve (AUC0-t ), AUC extrapolated to infinity (AUC0-∞ ), time to maximum concentration, and elimination half-life were estimated to prove bioequivalence. The confidence intervals for the log-transformed test/reference ratios for alfuzosin 110.7% (98.0-124.9) and 112.0% (101.9-123.1) for Cmax and AUC0-t respectively, which are within the allowed limits specified by the regulatory authorities (80-125% for Cmax and AUC0-t ). The test formulation can therefore be prescribed as an alternative to the reference for symptomatic treatment of benign prostatic hyperplasia.
Assuntos
Composição de Medicamentos/estatística & dados numéricos , Hiperplasia Prostática/tratamento farmacológico , Quinazolinas/farmacocinética , Agentes Urológicos/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Citocromo P-450 CYP3A/metabolismo , Composição de Medicamentos/métodos , Medicamentos Genéricos/farmacocinética , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Hiperplasia Prostática/sangue , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Equivalência Terapêutica , Agentes Urológicos/administração & dosagem , Agentes Urológicos/efeitos adversosRESUMO
BACKGROUND: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved ß3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. OBJECTIVE: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. RESULTS: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting ß3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.
Assuntos
Acetanilidas/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Tiazóis/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Acetanilidas/efeitos adversos , Acetanilidas/farmacocinética , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/farmacocinética , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/farmacocinética , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis/efeitos adversos , Tiazóis/farmacocinética , Agentes Urológicos/efeitos adversos , Agentes Urológicos/farmacocinéticaRESUMO
Studies reported that Serenoa repens was effective in relieving lower urinary tract symptoms (LUTS). This article carried out a systematic review and meta-analysis to compare Serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia (BPH) after at least 6-month treatment cycle. Four studies involving 1,080 patients (543 in the Serenoa repens group and 537 in the tamsulosin group) were included in the meta-analysis. The results were as follows: compared with tamsulosin, Serenoa repens had a same effect in treating BPH in terms of International Prostate Symptom Score (IPSS) (mean difference [MD] 0.63, 95% confidence interval [CI] [-0.33, 1.59], p = 0.20), quality of life (QoL) (MD 1.51, 95% CI [-1.51, 4.52], p = 0.33), maximum flow rate (Qmax) (MD 0.27, 95% CI [-0.15, 0.68], p = 0.21), postvoid residual volume (PVR) (MD -4.23, 95% CI [-22.97, 14.44], p = 0.65), prostate-specific antigen (PSA) (MD 0.46, 95% CI [-0.06, 0.97], p = 0.08) with the exception of prostate volume (PV) (MD -0.29, 95% CI [-0.41, -0.17], p < 0.00001). For side effects, Serenoa repens was well tolerated compared with tamsulosin especially in ejaculation disorders (odds ratio [OR] = 12.56, 95% CI [3.83, 41.18], p < 0.0001) and decreased libido (OR = 5.40; 95% CI [1.17, 24.87]; p = 0.03). This study indicated that Serenoa repens had the same effect in treating BPH compared with tamsulosin in terms of IPSS, QoL, and PVR after at least 6-month treatment cycle, however, the latter had a greater improvement in PV compared with the former. And Serenoa repens did not increase the risk of adverse events especially with respect to ejaculation disorders and libido decrease.