Biliary excretion of mitomycin C dextran conjugates in relation to physicochemical characteristics of carrier dextran.
- 1 January 1990
- journal article
- research article
- Published by Pharmaceutical Society of Japan in Journal of Pharmacobio-Dynamics
- Vol. 13 (7), 441-447
- https://doi.org/10.1248/bpb1978.13.441
Abstract
Biliary excretion characteristics of polymeric prodrugs of mitomycin C (MMC), mitomycin C-dextran conjugates with cationic or anionic charge (MMC-Dcat, MMC-Dan) and with different molecular weights of dextran (10,000, 70,000, and 500,000) were studied in rat. Following intravenous injection, bile was periodically collected and concentrations of free and dextran-conjugated MMC in it were determined by bioassay. MMC administered as a free form was excreted rapidly into bile and 1.8% of the dose was recovered within 2 h. A small amount of MMC was gradually excreted into bile after administration of all MMC-Ds and total recovery at 8 h was less than 1% of dose. In this case, a major part of excreted MMC was recovered as a conjugated form. MMC-Dcat gave a larger total excretion of MMC than MMC-Dan and excretion was also affected by the molecular weight of carrier dextran. The biliary recovery of MMC-Dcat labeled with 14C at a spacer moiety was significantly higher than that of conjugated MMC determined by bioassay suggesting release and/or inactivation of MMC in MMC-D during the circulation in the body. These results were compared with biliary excretion of model macromolecules with the same molecular weight but different electric charge in order to clarify the effect of electric charge on the biliary excretion of macromolecules. Cationic macromolecules exhibited higher biliary excretion in relation to greater hepatic uptake.This publication has 13 references indexed in Scilit:
- Development of a novel polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate with anionic charge. II. Disposition and pharmacokinetics following intravenous and intramuscular administrationInternational Journal of Pharmaceutics, 1987
- Development of a novel polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate with anionic charge. I. Physicochemical characteristics and in vivo and in vitro antitumor activitiesInternational Journal of Pharmaceutics, 1987
- Urinary excretion characteristics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate.Journal of Pharmacobio-Dynamics, 1985
- DISPOSITION AND PHARMACOKINETICS OF A POLYMERIC PRODRUG OF MITOMYCIN-C, MITOMYCIN-C-DEXTRAN CONJUGATE, IN THE RAT1984
- The preparation and labeling of DTPA-coupled albuminThe International Journal of Applied Radiation and Isotopes, 1982
- Physico-chemical and antitumor characteristics of high molecular weight prodrugs of Mitomycin C.CHEMICAL & PHARMACEUTICAL BULLETIN, 1982
- Mitomycin C-dextran conjugate: a novel high molecular weight pro-drug of mitomycin CJournal of Pharmacy and Pharmacology, 1980
- A simplified method of sample preparation for determination of tritium, carbon-14, or sulfur-35 in blood or tissue by liquid scintillation countingAnalytical Biochemistry, 1966
- A basic derivative of dextran and its interaction with serum albuminBiochemical Journal, 1960
- Chromatography of Proteins. I. Cellulose Ion-exchange AdsorbentsJournal of the American Chemical Society, 1956