Cysyk R L, Shoemaker D D, Ayers O C, Adamson R H
Pharmacology. 1978;16(4):206-13. doi: 10.1159/000136768.
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.
4'-（9-吖啶基氨基）-甲磺酰间茴香胺（AMSA）是一种目前正在进行临床评估的新型抗肿瘤药物，本研究观察了其经口给药后在小鼠和大鼠体内的处置情况，并与静脉给药后的情况进行了比较。AMSA的代谢命运在静脉给药和经口给药时是相同的；然而，AMSA在两种给药途径之间的组织分布存在显著差异。经胃肠道吸收后，AMSA迅速被肝脏从血浆中清除，并作为代谢产物经胆汁排泄。口服给药后，肝脏中AMSA的浓度相对较高，足以对植入该部位的L1210细胞产生细胞毒性作用。结果表明，口服AMSA可在肝脏中实现选择性定位，同时降低全身暴露，这可能对肝转移瘤或原发性肝细胞癌有用。
