Abstract
Now that several formulations of botulinum toxin type-A (BoNT-A) are on the market in North America and throughout the world, it is of great practical importance for those who administer these medications to be familiar with the differences between the formulations. These differences pertain to the stability of the medications, in particular during the period of time between reconstitution and administration, which may affect the degree of diffusion through various tissues after injection. A variety of relatively new uses of BoNT-A for dermatological conditions will be discussed.
Introduction
Medicines formulated from the highly purified, naturally occurring protein known as botulinum toxin type-A (BoNT-A) have been in use since 1980, when ophthalmologist Alan Scott used an injectable formulation of BoNT-A to treat strabismus and blepharospasm in humans. The first formulation of BoNT-A to become commercially available was onabotulinumtoxinA (BOTOX®), licensed in the United States in 1989 for treatment of three conditions: strabismus, blepharospasm, and hemifacial spasm. In recent years, two other formulations of BoNT-A have been licensed for use in the United States and a number of other countries: abobotulinumtoxinA (Dysport®) and incobotulinumtoxinA (XEOMIN®).
Those interested in BoNT-A should become familiar with the non-proprietary names for the various formulations of BoNT-A, because increasingly, presentations at meetings and in scientific publications are using the non-proprietary rather than the trade names for these products.[1] A different non-proprietary name was assigned to each formulation of BoNT-A to reflect the fact that while the active ingredient in all three formulations is BoNT-A, the biological activity, in particular the stability and diffusion kinetics,[2,3] of the active ingredient is modulated by the other components of the formulation, notably the protective proteins (hemagglutinins and non-hemagglutinins, which are associated with BoNT-A in onabotulinumtoxinA and abobotulinumtoxinA) and the amount and type of human serum albumin (added to the formulations to keep the BoNT-A in solution after reconstitution). Biological activity is also affected by the manufacturing process (as each BoNT-A formulation is manufactured differently), as well as other excipients in the vial (e.g., sodium chloride and sucrose). The effects (if any) on stability after reconstitution caused by the presence of trypsin-like proteolytic activity in incobotulinumtoxinA[4] remain to be elucidated.
Kevin C. Smith, MD, FRCPC (Dermatology)
Skin Therapy Letter. 2011;16(8)
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