Objective: Detrusor hyperactivity with impaired contractility (DHIC) is not an uncommon bladder disorder, and is often difficult to treat. Therefore, using a rat model featuring both urinary frequency and residual uri...Objective: Detrusor hyperactivity with impaired contractility (DHIC) is not an uncommon bladder disorder, and is often difficult to treat. Therefore, using a rat model featuring both urinary frequency and residual urine, we investigated whether an anticholinergic agent (solifenacin) or a β3-agonist (mirabegron) is more suitable to combine with distigmine to treat DHIC. Methods: The partial bladder outlet obstruction (BOO) rat model was used. Rats were treated for 2 weeks: BOO/Solifenacin group was treated with 0.1 mg/kg solifenacin (n = 8), BOO/Mirabegron group was treated with 1 mg/kg mirabegron (n = 8), BOO/- group was not drug-treated but was given distilled water (n = 8), and the control group was also given distilled water (n = 8). Then the urethral ligature was removed under urethane anesthesia, and continuous cystometry was performed to evaluate bladder function. Baseline measurements were taken, then distigmine was administered to all groups, and cystometry was performed again to measure changes in bladder function. Results: Residual volumes increased in the BOO/- group, and the detrusor contractions were more frequent than that of the control group. Solifenacin treatment did not influence changes, except for threshold pressure, to any cystometric measurements. However, mirabegron treatment decreased the residual volume and residual volume rate;it also decreased detrusor contraction frequency similar to measurements obtained from the control group. Distigmine treatment enhanced detrusor contractions, which resulted in less residual volume, and decreased detrusor contraction frequency in the BOO model. Conclusions: The combination of distigmine and mirabegron was determined to be a better treatment than the combination of distigmine and solifenacin for DHIC.展开更多
<strong>Background: </strong>Though anticholinergic drugs are considered the standard treatment for neurogenic detrusor overactivity, it is far from an ideal tool, because of their adverse effects such as ...<strong>Background: </strong>Though anticholinergic drugs are considered the standard treatment for neurogenic detrusor overactivity, it is far from an ideal tool, because of their adverse effects such as Constipation or not respond sufficiently for a substantial proportion of patients. Recently mirabegron has become a commonly used overactive bladder medication in the general population, but few studies about mirabegron for the treatment of neurogenic detrusor overactivity. <strong>Objective:</strong> To evaluate the efficacy and safety of mirabegron for the treatment of neurogenic lower urinary tract dysfunction. <strong>Study Design:</strong> Prospective study. <strong>Methods:</strong> This prospective study included 13 adult patients with neurogenic lower urinary tract dysfunction as a result of spinal cord injury. All patients receiving mirabegron treatment (50 mg once daily) at least 6 weeks. The effective outcomes included the mean urine volume per catheterization, urinary incontinence episodes and Incontinence Specific Quality of Life Instrument. We monitored the blood pressure and heart rate to assess the cardiovascular safety, other adverse events were also recorded. <strong>Results:</strong> A total of 13 patients were included. After 6 weeks of treatment, all patients experienced a significant increase in the mean volume of per catheterization from 238.46 ± 65.43 ml to 327.69 ± 59.04 ml (p = 0.001). There is a significant reduction in the volume of urine leakage (463.85 ± 247.98 ml VS 180.00 ± 190.96 ml, p = 0.003) and incontinence episodes per 24 h (4.46 ± 2.03 VS 1.92 ± 1.50, p = 0.001). Significant improvement in mean Incontinence Specific Quality of Life Instrument was also found (p = 0.001). No patients reported dry mouth during the study, and the cardiovascular safety were acceptable. <strong>Conclusion:</strong> Mirabegron is safe and effective in the treatment of neurogenic lower urinary tract dysfunction. It might be a good choice for reducing the cessation of clean intermittent catheterization.展开更多
Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, ...Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, the antimuscarinic drugs. This fi rst-in-class, potent β3-adrenoceptors agonist has recently received approval by regulatory authorities in Japan, United States and Europe, based on the favourable efficacy-tolerability profile demonstrated in multiple randomized, multinational, controlled trials, both short and long-term. There is substantial consistency through the studies in reporting the cardiovascular safety of treatment with mirabegron. The main advantage of mirabegron is the placebo-like incidence of classic adverse effects caused by antimuscarinics, dry mouth and constipation, that is expected to improve long-term adherence of patients to treatment. Mirabegron can be used in patients with contraindications to antimuscarinics and in those who discontinued previous antimuscarinic therapy. Herein, we reviewed the published literature on mirabegron, focusing on the rationale of β3-agonism for OAB treatment and on the preclinical and clinical evidence of effi cacy and safety available on this new pharmacological principle.展开更多
文摘Objective: Detrusor hyperactivity with impaired contractility (DHIC) is not an uncommon bladder disorder, and is often difficult to treat. Therefore, using a rat model featuring both urinary frequency and residual urine, we investigated whether an anticholinergic agent (solifenacin) or a β3-agonist (mirabegron) is more suitable to combine with distigmine to treat DHIC. Methods: The partial bladder outlet obstruction (BOO) rat model was used. Rats were treated for 2 weeks: BOO/Solifenacin group was treated with 0.1 mg/kg solifenacin (n = 8), BOO/Mirabegron group was treated with 1 mg/kg mirabegron (n = 8), BOO/- group was not drug-treated but was given distilled water (n = 8), and the control group was also given distilled water (n = 8). Then the urethral ligature was removed under urethane anesthesia, and continuous cystometry was performed to evaluate bladder function. Baseline measurements were taken, then distigmine was administered to all groups, and cystometry was performed again to measure changes in bladder function. Results: Residual volumes increased in the BOO/- group, and the detrusor contractions were more frequent than that of the control group. Solifenacin treatment did not influence changes, except for threshold pressure, to any cystometric measurements. However, mirabegron treatment decreased the residual volume and residual volume rate;it also decreased detrusor contraction frequency similar to measurements obtained from the control group. Distigmine treatment enhanced detrusor contractions, which resulted in less residual volume, and decreased detrusor contraction frequency in the BOO model. Conclusions: The combination of distigmine and mirabegron was determined to be a better treatment than the combination of distigmine and solifenacin for DHIC.
文摘<strong>Background: </strong>Though anticholinergic drugs are considered the standard treatment for neurogenic detrusor overactivity, it is far from an ideal tool, because of their adverse effects such as Constipation or not respond sufficiently for a substantial proportion of patients. Recently mirabegron has become a commonly used overactive bladder medication in the general population, but few studies about mirabegron for the treatment of neurogenic detrusor overactivity. <strong>Objective:</strong> To evaluate the efficacy and safety of mirabegron for the treatment of neurogenic lower urinary tract dysfunction. <strong>Study Design:</strong> Prospective study. <strong>Methods:</strong> This prospective study included 13 adult patients with neurogenic lower urinary tract dysfunction as a result of spinal cord injury. All patients receiving mirabegron treatment (50 mg once daily) at least 6 weeks. The effective outcomes included the mean urine volume per catheterization, urinary incontinence episodes and Incontinence Specific Quality of Life Instrument. We monitored the blood pressure and heart rate to assess the cardiovascular safety, other adverse events were also recorded. <strong>Results:</strong> A total of 13 patients were included. After 6 weeks of treatment, all patients experienced a significant increase in the mean volume of per catheterization from 238.46 ± 65.43 ml to 327.69 ± 59.04 ml (p = 0.001). There is a significant reduction in the volume of urine leakage (463.85 ± 247.98 ml VS 180.00 ± 190.96 ml, p = 0.003) and incontinence episodes per 24 h (4.46 ± 2.03 VS 1.92 ± 1.50, p = 0.001). Significant improvement in mean Incontinence Specific Quality of Life Instrument was also found (p = 0.001). No patients reported dry mouth during the study, and the cardiovascular safety were acceptable. <strong>Conclusion:</strong> Mirabegron is safe and effective in the treatment of neurogenic lower urinary tract dysfunction. It might be a good choice for reducing the cessation of clean intermittent catheterization.
文摘Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, the antimuscarinic drugs. This fi rst-in-class, potent β3-adrenoceptors agonist has recently received approval by regulatory authorities in Japan, United States and Europe, based on the favourable efficacy-tolerability profile demonstrated in multiple randomized, multinational, controlled trials, both short and long-term. There is substantial consistency through the studies in reporting the cardiovascular safety of treatment with mirabegron. The main advantage of mirabegron is the placebo-like incidence of classic adverse effects caused by antimuscarinics, dry mouth and constipation, that is expected to improve long-term adherence of patients to treatment. Mirabegron can be used in patients with contraindications to antimuscarinics and in those who discontinued previous antimuscarinic therapy. Herein, we reviewed the published literature on mirabegron, focusing on the rationale of β3-agonism for OAB treatment and on the preclinical and clinical evidence of effi cacy and safety available on this new pharmacological principle.
