Preclinical Toxicologic Evaluation of 4'-(9-Acridinylamino)Methanesulphon-m-Anisidide Monochloride in Mice,Dogs and Monkeys.

摘要

Combined IV LD50of m-AMSA in male and female CDF1mice was 101mg/sq m. Major target organ in mice was the liver. In dogs and monkeys,the drug produced toxic effects on CNS,gastrointestinal tract,liver,kidney,lymphoid tissue and bone marrow. CNS and renal toxicity were present only after administration of single lethal doses. Clinical signs of hepatotoxicity were most severe in dogs after single doses,and showed a delayed onset after multiple dose treatments. Monkeys were less sensitive than the dog to the hepatotoxic effects of the drug and were the least sensitive of the large animal species. Toxic effects on the bone marrow were reversible but histopathologic changes in lymphoid tissue and liver were present 45days after treatment. In dogs, a five daily dose schedule produced greater toxicity than single push injections;attenuation of toxic response occurred when rest periods were introduced between repeated doses or the daily dose was reduced.