Botulinum A toxin: Dysport improvement of biological availability.
We investigated the efficacy and potency of Dysport, a botulinum neurotoxin type A complex approved for therapy, under various conditions. Conditions for maximal expression of biological activity were explored in vitro in the phrenic nerve-hemidiaphragm preparation, while conditions for optimal distribution of the toxin were tested in vivo in a double blind trial involving volunteers, using the foot Muscles extensor digitorum brevis. In contrast to the recommendations of the manufacturer, the biological availability of Dysport could be enhanced by (1) lowering its concentration, (2) supplementing with albumin, and (3) increasing the injection volume. On the basis of these experimental findings Dysport was diluted to a final concentration of 50 U/ml for therapeutic purposes. In a blind, single crossover study patients suffering from various forms of dystonia were treated with Dysport, first diluted and dosed as suggested by the manufacturer and then with doses cut by approximately 70% in accordance with the experimental findings. The low-dose treatment was as effective as the treatment with the recommended higher doses, but side effects were considerably less apparent. The benefits to be derived from these adjustments include a low risk of antibody formation, which could preclude continued or future treatment and substantial cost savings.
Bigalke
H
H
Department of Pharmacology and Toxicology, Medical School of Hannover, 30623 Hannover, Germany.
Wohlfarth
K
K
Irmer
A
A
Dengler
R
R
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001682:Biological Availability; D001764:Blepharospasm / Q000188:drug therapy; D019274:Botulinum Toxins, Type A / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003964:Diaphragm / Q000294:innervation; D004311:Double-Blind Method; D004421:Dystonia / Q000188:drug therapy; D004558:Electric Stimulation; D005260:Female; D019569:Hemifacial Spasm / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D019274:Botulinum Toxins, Type A