Article ID Journal Published Year Pages File Type
3924225 European Urology 2012 8 Pages PDF
Abstract

BackgroundTwo botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable.ObjectiveAssessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO.Design, setting, and participantsFemale, adult, Sprague-Dawley rats (n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats.MeasurementsVoiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test.Results and limitationsMEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively).ConclusionsThis is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.

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