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Pharmakologische Aspekte therapeutischer Botulinum-Toxin-Präparationen

Pharmacological aspects of therapeutic botulinum toxin preparations

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Zusammenfassung

Therapeutische Präparationen von Botulinum-Toxin (BT) bestehen aus Botulinum-Neurotoxin (BNT), Komplexproteinen und pharmazeutischen Hilfsstoffen. Je nach Zielgewebe kann BT die cholinerge neuromuskuläre Transmission zu extrafusalen und intrafusalen Muskelfasern oder die cholinerge autonome Transmission zu Schweißdrüsen, Tränendrüsen, Speicheldrüsen und glatter Muskulatur unterbrechen. Indirekte Effekte auf das Zentralnervensystem sind zahlreich, direkte sind nach intramuskulärer Injektion bisher nicht beschrieben worden. BT Typ A wird als Botox, Dysport, Xeomin, Hengli/CBTX-A und Neuronox, BT Typ B als NeuroBloc/Myobloc angeboten. Nebenwirkungen der BT-Therapie können obligat, lokal und systemisch sein. Die Nebenwirkungsprofile der verschiedenen BT-Typ-A-Präparationen sind weitgehend identisch. Bei BT Typ B zeigen sich häufig zusätzlich systemische autonome Nebenwirkungen. Langzeitbehandlungen rufen keine zusätzlichen Nebenwirkungen hervor. Gegen BNT können Antikörper gebildet werden, die die biologische BNT-Wirkung ganz oder teilweise blockieren. Das Risiko einer BNT-Antikörper-Bildung hängt wesentlich ab von der BNT-Menge, die bei jeder BT-Injektions-Serie appliziert wird, vom Intervall zwischen den BT-Injektions-Serien und von der spezifischen biologischen Aktivität (SBA) der BT-Präparation. Diese beträgt bei NeuroBloc 5 MU-E/ng BNT, bei Botox 60, bei Dysport 100 und bei Xeomin 167. Xeomin dürfte daher die günstigsten Antigenitätseigenschaften aufweisen. Entsprechende klinische Erfahrungen stehen jedoch noch aus.

Summary

Therapeutic preparations of botulinum toxin (BT) consist of botulinum neurotoxin (BNT), complexing proteins, and excipients. Depending on the target tissue, BNT can block cholinergic neuromuscular innervation of intra- and extrafusal muscle fibres or cholinergic autonomic innervation of sweat, lacrimal, and salival glands and smooth muscles. Indirect CNS effects are numerous; direct ones have not been reported after intramuscular application. Botulinum toxin type A is distributed as Botox, Dysport, Xeomin, Hengli/CBTX-A, and Neuronox and BT type B as NeuroBloc/Myobloc. Differences in potency labelling of therapeutic BT preparations can be corrected by introduction of a conversion factor of 1:3 between Botox and Dysport, of 1:1 between Botox and Xeomin, and of 1:40 between Botox and NeuroBloc/Myobloc. Acute adverse effects of BT can be obligate, local or systemic. Adverse effect profiles of the different preparations are similar. However, BT type B frequently produces additional autonomic systemic adverse effects. Long-term application does not produce additional adverse effects. BNT can be partially or completely blocked by antibodies. Risk factors include the amount of BNT applied at each injection series, the interval between injection series, and the specific biological potency (SBP) of the BT preparation used. The SBP is 5 equivalent mouse units/ng BNT for NeuroBloc, 60 for Botox, 100 for Dysport, and 167 for Xeomin. Xeomin should therefore have a particularly low antigenicity. Clinical confirmation of this predicition, however, is lacking.

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  1. Klinik und Poliklinik für Neurologie, Universität Rostock, Gehlsheimer Straße 20, 18147, Rostock

    D. Dressler

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Dressler, D. Pharmakologische Aspekte therapeutischer Botulinum-Toxin-Präparationen. Nervenarzt 77, 912–921 (2006). https://doi.org/10.1007/s00115-006-2090-2

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