Oral absorption and selective tissue localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide.
The disposition of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA), a new antitumor agent presently undergoing clinical evaluation, was studied in mice and rats following oral administration and compared to that observed following intravenous administration. The metabolic fate of  AMSA was the same with either intravenous or oral administration; however, the tissue distribution of AMSA differed significantly between the two routes of administration. Following absorption from the GI tract, AMSA was rapidly cleared from plasma by the liver and excreted in the bile as metabolites. Concentrations of AMSA in the liver were relatively high after oral administration and were sufficient to exert a cytotoxic effect on L1210 cells implanted at the site. The results indicate the use of AMSA orally to attain selective localization in the liver with decreased systemic exposure, which may prove useful against tumor metastases to the liver or primary hepatocellular carcinoma.
D000042:Absorption; D000166:Acridines / Q000008:administration & dosage / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D001681:Biological Assay; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D002845:Chromatography; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010655:Phenylenediamines / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D000166:Acridines; D000970:Antineoplastic Agents; D010655:Phenylenediamines