THE MEDIAN PARALYSIS UNIT - A MORE PHARMACOLOGICALLY RELEVANT UNIT OF BIOLOGIC ACTIVITY FOR BOTULINUM TOXIN

摘要

Although the LD(50) has been used to quantify the biologically active toxin in clinical preparations of botulinum A toxin (Botox(R) and Dysport(R)), a discrepancy exists between the clinical potency of equivalent international units Of different formulations of botulinum A toxin for multiple clinical indications. Our laboratory previously reported that a regional chemodenervation assay in the mouse could be utilized to detect the difference in the potencies of the clinical preparations of toxin [Pearce et al. (1994) Toxic. appl. Pharmac. 128, 69-77]. The purpose of this study was to quantify the regional paralysis produced by botulinum toxin and define a new pharmacologic/biologic unit of activity that more accurately reflects the mechanism of action of botulinum toxin in the clinical setting. Quantal analysis of regional paralysis revealed that the ED(50), defined as the median paralysis unit (MPU) for Botox(R) and Dysport(R), was 0.41 +/- 0.01 and 1.00 +/- 0.02 LD(50) units, respectively. Differences in the potencies found in retrospective clinical studies comparing Botox(R) and Dysport(R) were accurately reflected, for the first time, by the dose of toxin expressed in terms of the MPU (median paralysis unit). The data suggested that the MPU may be a more appropriate measure of the biologic activity in therapeutic formulations of botulinum toxin. [References: 33]