DISPOSITION AND PHARMACOKINETICS OF A POLYMERIC PRODRUG OF MITOMYCIN-C, MITOMYCIN-C-DEXTRAN CONJUGATE, IN THE RAT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (4) , 492-499
Abstract
The disposition and pharmacokinetics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMCD [an anticancer drug]), following i.v. bolus administration were studied in rats. Three types of MMCD, conjugates with dextran of MW of 10,000, 70,000 and 500,000, were tested and disposition of carrier dextran and MMC was determined by 14C radioactivity counting and bioassay, respectively. Radioactivity was accumulated in the RES such as the liver, spleen and lymph nodes after injection of all 3 types of 14C-MMCD, but not in the lung, heart and muscle. Renal distribution of 14C-MMCD varied with the molecular size of the carrier. After injection of cold MMCD, plasma concentrations of MMC in the free and conjugated forms were determined separately on the bases of bioassay. Similar sustained plasma levels of MMC were detected regardless of the carrier size although the concentration-time profiles of MMCD varied with the size of dextran. These plasma concentration data were fitted to a compartment model including a first order conversion process from MMCD to MMC in the central and peripheral compartments of MMCD. Kinetical analysis revealed that MMCD acts as a reservoir of MMC which behaves characteristically as a macromolecule while supplying active MMC in the body.

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