title: Minimal effective dose of dysport and botox in a rat model of neurogenic detrusor overactivity.
abstract: BACKGROUND
  Two 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.
  
  
  OBJECTIVE
  Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord-injured (SCI) rats with NDO.
  
  
  METHODS
  Female, adult, Sprague-Dawley rats (n=98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25μl 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.
  
  
  METHODS
  Voiding 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.
  
  
  CONCLUSIONS
  MEDs 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±0.3mm 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±0.6mm 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).
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Pelvipharm, Orsay, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Oger
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pignol
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pham
authors.forename: Amélie
authors.initials: A
authors.lastname: Le Maux
authors.forename: Pierre-Etienne
authors.initials: PE
authors.lastname: Chabrier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Caisey
authors.forename: Sandrine
authors.initials: S
authors.lastname: Compagnie
authors.forename: Philippe
authors.initials: P
authors.lastname: Picaut
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernabé
authors.forename: Laurent
authors.initials: L
authors.lastname: Alexandre
authors.forename: François
authors.initials: F
authors.lastname: Giuliano
authors.forename: Pierre
authors.initials: P
authors.lastname: Denys
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology; D016896:Treatment Outcome; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014554:Urination / Q000187:drug effects / Q000502:physiology
chemical_list: D019274:Botulinum Toxins, Type A; C542869:abobotulinumtoxinA