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aboBoNTA(保妥适®)膀胱逼尿肌注射位点数量的减少对神经源性逼尿肌过度活动大鼠模型的疗效和安全性有影响吗?

Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?

作者信息

Huynh Le Maux Amélie, Pignol Bernadette, Behr-Roussel Delphine, Blachon Jean-Luc, Chabrier Pierre-Etienne, Compagnie Sandrine, Picaut Philippe, Bernabé Jacques, Giuliano François, Denys Pierre

机构信息

Pelvipharm, 2 avenue de la source de la Bièvre, Bâtiment Simone Veil, Université de Versailles-Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux 78180, France.

Unité de Formation et de Recherche des Sciences de la Santé, Université de Versailles-Saint-Quentin-en-Yvelines, Institut National de la Santé Et de la Recherche Médicale U1179, Montigny-le-Bretonneux 78180, France.

出版信息

Toxins (Basel). 2015 Dec 17;7(12):5462-71. doi: 10.3390/toxins7124896.

Abstract

Intradetrusor injections of Botulinum toxin A-currently onabotulinumtoxinA-is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport(®) abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder.

摘要

膀胱逼尿肌内注射A型肉毒毒素(目前是onabotulinumtoxinA)被注册为治疗神经源性逼尿肌过度活动(NDO)的二线治疗方法。常见的临床做法是在逼尿肌内进行30次×1 mL注射;然而,方案仍存在差异,需要标准化。在脊髓损伤大鼠(SCI)中评估了减少Dysport(®)a型肉毒杆菌毒素(aboBoNTA)注射部位数量的效果。脊髓损伤后19天,雌性大鼠接受膀胱逼尿肌内注射生理盐水或22.5 U的aboBoNTA,分别分布在四个或八个部位。注射后两天,对清醒大鼠进行连续膀胱测压。根据临床相关参数评估22.5 U的aboBoNTA与汇总生理盐水组的疗效:最大压力、膀胱容量、顺应性、排尿效率,以及非排尿收缩(NVC)的幅度、频率和容量阈值。22.5 U的aboBoNTA显著降低了最大压力,但不影响排尿效率。在四个部位注射时,aboBoNTA显著增加了膀胱容量和顺应性,而在八个部位注射时仅增加了顺应性。aboBoNTA显著降低了NVC的频率和幅度。这项临床前研究表明,尽管减少了注射部位数量,但aboBoNTA仍具有相似的抑制作用。有必要进行进一步研究以优化给药方案,从而提高基于肉毒杆菌毒素A的治疗方式对NDO和特发性膀胱过度活动症的风险效益比。

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