Botulinum toxin A: is it really that fragile a molecule?

BACKGROUND Botulinum toxin A is considered to be an extremely fragile molecule, with recommended usage of some reconstituted botulinum toxin A formulations within 4 hours of reconstitution. Extreme caution is recommended to avoid agitation of the vial. OBJECTIVE To determine whether the effect of reconstituted botulinum toxin A is maintained even when it is agitated vigorously. DESIGN Experimental, comparative, animal study. PARTICIPANTS Sixty-four white Swiss Webster mice, aged 2 to 4 weeks, arranged in eight separate groups. INTERVENTION Reconstituted onabotulinumtoxinA (2.5 U/0.1 mL) was placed securely in a battery-operated mechanized apparatus. The apparatus with the vial was placed in the refrigerator, and the apparatus continuously inverted and straightened the onabotulinumtoxinA vial 30 times a minute. Eight mice were each injected intraperitoneally with 1 U of the agitated onabotulinumtoxinA on days 1, 3, 5, 7, 14, 21, 28, and 42, to evaluate the efficacy of the continuously agitated onabotulinumtoxinA. MAIN OUTCOME MEASURE Death of the mice, demonstrating efficacy of the onabotulinumtoxinA molecule. RESULTS Half of each group of mice (4/8 mice) died within 48 hours of the injection (range 16-48 hours). CONCLUSION The effect of botulinum toxin type A is maintained even when it is agitated vigorously for up to 6 weeks. The authors have indicated no significant interest with commercial supporters.