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新药物制剂及其治疗尿失禁疗效的近期临床研究。

Recent clinical studies of new pharmacologic agents and their efficacy in the treatment of incontinence.

作者信息

Appell R A

出版信息

Rev Urol. 2001;3 Suppl 1(Suppl 1):S15-8.

Abstract

Two agents for the control of overactive bladder-tolterodine (TOL) and extended-release oxybutynin (Oxy-XL)-have been evaluated in a number of studies for their efficacy in urge incontinence. Studies have demonstrated that TOL achieved a 20% reduction in the frequency of voiding and a 45% reduction in urge incontinent episodes. Efficacy was comparable between TOL and immediate-release oxybutinin (Oxy-IR), the standard anticholinergic comparator. There is a delay of some weeks in achieving relief with TOL, but thereafter there is a continued decrease in the total number of both micturitions and incontinent episodes in 24 hours. Trials demonstrated that there were no safety concerns at all with TOL. In particular, there was a lower incidence of dry mouth with TOL than with Oxy-IR. Dose-ranging studies established that TOL produced the lowest incidence of side effects while maintaining efficacy. In a long-term, community-use study of Oxy-XL, there was a very low incidence of central nervous system side effects, including mental acuity and memory. Among elderly nursing home patients, Oxy-XL achieved a 90% reduction in weekly urge incontinence episodes and an 86% decrease in pad use. Oxy-XL was shown to cause a significantly lower reduction in salivary output than Oxy-IR and TOL. In a recent head-to-head comparison study, there were significant differences found between Oxy-XL and TOL. Other studies have shown that the administration of Oxy-XL results in a significantly lower production of the metabolites responsible for anticholinergic side effect, particularly dry mouth, than with the standard release form, owing largely to the elimination of a first-pass effect. A long-acting form of TOL resulted in a 53% reduction in incontinent episodes. Both these anticholinergic agents have been shown to have excellent efficacy and tolerability. But the future of OAB therapy lies in targeting other mechanisms responsible for incontinence.

摘要

两种用于控制膀胱过度活动症的药物——托特罗定(TOL)和缓释奥昔布宁(Oxy-XL)——已在多项研究中对其在急迫性尿失禁方面的疗效进行了评估。研究表明,TOL使排尿频率降低了20%,急迫性尿失禁发作次数减少了45%。TOL与标准抗胆碱能对照药物即速释奥昔布宁(Oxy-IR)的疗效相当。使用TOL缓解症状会有几周的延迟,但此后24小时内排尿次数和失禁发作总数会持续减少。试验表明,TOL完全没有安全性问题。特别是,与Oxy-IR相比,TOL导致口干的发生率更低。剂量范围研究确定,TOL在保持疗效的同时副作用发生率最低。在一项关于Oxy-XL的长期社区使用研究中,中枢神经系统副作用(包括精神敏锐度和记忆力)的发生率非常低。在老年疗养院患者中,Oxy-XL使每周急迫性尿失禁发作次数减少了90%,护垫使用量减少了86%。结果显示,Oxy-XL导致唾液分泌减少的程度明显低于Oxy-IR和TOL。在最近一项直接比较研究中,发现Oxy-XL和TOL之间存在显著差异。其他研究表明,与标准释放剂型相比,使用Oxy-XL产生导致抗胆碱能副作用(尤其是口干)的代谢物的量显著更低,这主要是由于消除了首过效应。一种长效形式的TOL使失禁发作次数减少了53%。这两种抗胆碱能药物均已显示出优异的疗效和耐受性。但膀胱过度活动症治疗的未来在于针对导致尿失禁的其他机制。

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