Plasma Disposition and in Vivo and in Vitro Antitumor Activities of Mitomycin C-Dextran Conjugate in Relation to the Mode of Action

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In order to clarify the factors dominating the antitumor effects of mitomycin C-dextran conjugates (MMC-D), the plasma disposition of MMC-D in rats, and the in vivo and in vitro antitumor activities were studied in comparison with those of mitomycin C. Three types of MMC-D, conjugates with dextran having molecular weights of 10000,70000 and 500000,were administered to rats by intravenous, intramuscular and intraperitoneal injection, and the plasma concentrations of MMC were determined by bioassay. Similar sustained plasma levels of MMC after injection of MMC-D were obtained regardless of carrier size or administration route. Intraperitoneal injection of MMC-D significantly improved the survival time of mice bearing L1210 leukemia, while intravenous or intramuscular injection did not. MMC-D showed higher maximum activity at a lower dose as its molecular size increased. L1210 leukemia cells were exposed to MMC-D for 1 h in vitro and cytocidal activities were evaluated in terms of the survival time of mice inoculated with treated cells, or the growth rate of cells in a cell culture system. MMC-D exhibited different cytocidal activities depending on its molecular weight in these systems whereas MMC-D was considered to liberate MMC at the same rate regardless of molecular weight in vitro. These results suggest that MMC-D has some direct interaction with tumor cells and this interaction plays an important role in the manifestation of antitumor activity in vivo, as well as a modified pharmacokinetic behavior in the body.
公益社団法人日本薬学会の論文
1985-07-25

Plasma Disposition and in Vivo and in Vitro Antitumor Activities of Mitomycin C-Dextran Conjugate in Relation to the Mode of Action

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