TOXICITY AND TOLERANCE STUDIES ON AET
Attempts were made to develop administration schedules that would lower the toxicity of the radioprotective agent 2-aminoethylisothiouronium bromide hydrobromide (AET) by studies in rats, rabbits, and dogs. The acute intraperitoneal LD/sub 50/ for this agent in these species was 288, 236 and approximates 113 mg/kg, respectively. Repeated and increasing intraperitoneal doses of AET in rats over 14 days allowed the animals to tolerate a 25% larger dose. A similar tolerance was obtained with the dog over 12 to 20 days but not with the rabbit over 7 days. A radioprotective dose of AET in the rat to double the tolerated x-ray or gamma -ray dose is approximates 300 mg/kg. The tolerance developed to AET in the dog or rabbit was not great enough to reach such a dose of AET. Symptoms of AET toxicity are described for rats, dogs, and rabbits. Dogs receiving AET intraperitoneally suffered from lesions at the site of injection and showed marked wt loss while dogs receiving repeated oral doses of AET were healthier and better tolerated the intraperitoneal challenging dose of 200 mg/kg. Development of tolerance to intraperitoneal doses was 25%, and similar results were obtained when 0.25 mg/kg of atropine sulfate was given concomitantly with the AET. At autopsy, gross examination of the dogs revealed only drug-induced changes at the site of injection, such as ulcerations in the peritoneum and surrounding abdominal muscles. (TCO)
- Research Organization:
- Univ. of Arkansas, Little Rock
- NSA Number:
- NSA-17-033514
- OSTI ID:
- 4664667
- Journal Information:
- Arch. Intern. Pharmacodyn., Journal Name: Arch. Intern. Pharmacodyn. Vol. Vol: 142
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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