Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125I-botulinum-free neurotoxin: time course of tissue distribution.
The diffusion from the site of intramuscular injection of 900 kDa botulinum neurotoxin-hemagglutinin complex (BoNT/A-complex) and 150 kDa free-botulinum neurotoxin (free-BoNT/A) was compared. Radioiodinated compounds were injected into the gastrocnemius muscle of rats (70Units (U) 125I-BoNT/A-complex, 67 or 344 U free-125I-BoNT/A, or free-125I-iodide) and the eyelids of rabbits (24 U 125I-BoNT/A-complex or 108 U free-125I-BoNT/A), and measured in various tissues at different time points. There were no detectable systemic effects or generalized botulinum neurotoxin toxicity in either rats or rabbits, indicating that most of the toxin, whether as 125I-BoNT/A-complex or free-125I-BoNT/A, remained at the injection site. In rats, 125I-BoNT/A-complex and free-125I-BoNT/A diffused in a pattern that was grossly similar. Almost no radioactivity was recovered from the brain. Radioactivity recovered from distant tissues (thyroid, skin, and contralateral muscle) was primarily attributable to either low molecular weight 125I-containing peptides or 125I-iodide. After injection into rabbit eyelids, neither 125I-BoNT/A-complex nor free-125I-BoNT/A spread to distant structures, including the eye. The results indicate that most of the neurotoxin does not diffuse from the injection site, whether in free or complexed form, and this may reduce the potential for systemic effects.
Tang-Liu
Diane D-S
DD
Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., 2525 Dupont Drive, RD2-2B, Irvine, CA 92715, USA. tang-liu_diane@allergen.com
Aoki
K Roger
KR
Dolly
J Oliver
JO
de Paiva
Anton
A
Houchen
Tara L
TL
Chasseaud
Leslie F
LF
Webber
Colin
C
D000818:Animals; D001905:Botulinum Toxins / Q000493:pharmacokinetics*; D019274:Botulinum Toxins, Type A / Q000493:pharmacokinetics*; D004058:Diffusion; D005143:Eyelids / Q000187:drug effects; D007273:Injections, Intramuscular; D007457:Iodine Radioisotopes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A