BOTULINUM TOXIN TYPE-A - FROM TOXIN TO THERAPEUTIC AGENT

Botulinum toxin is one of the most potent toxins available. Yet despit e its toxic qualities, it has proved to be a remarkable therapeutic ag ent when used appropriately. The chemical complexity of this substance , combined with its extreme potency and the limits of analytical sensi tivity, restrict the opportunity to study its pharmacokinetic profile, particularly in humans. The results of animal studies suggest that th e botulinum toxin type A complex remains concentrated at the site of i ntramuscular injection for some time before entering the systemic circ ulation. It is then quickly metabolized to simpler molecular structure s and excreted mainly in the urine. The distribution of the complex to other systemic tissues is limited. No intact neurotoxin was detected in the spinal cord of rats in these studies. Preclinical safety studie s of this botulinum toxin in various animal species have shown no note worthy adverse local or systemic effects following intramuscular admin istration at clinically relevant dose levels. Overall, the preclinical safety profile indicates that doses of up to 6 U/kg are well tolerate d in adults and children. These preclinical data are consistent with t he safety profile reported in clinical studies. Progress is currently being made towards the development of a sensitive bioassay to measure levels of neutralizing antibodies to the toxin.