Conversion of mitomycin C to 2,7-diaminomitosene and 10-decarbamoyl 2,7-diaminomitosene in tumour tissue in vivo

Cancer Chemother Pharmacol. 1995;35(4):318-22. doi: 10.1007/BF00689451.

Abstract

The progress of mitomycin C (MMC) bioreduction was studied in vivo in the rat Sp 107 mammary carcinoma after intra-tumoural injection of either 100 micrograms or 1 mg. 2,7-Diaminomitosene (2,7-DM) was utilised as a primary bioreductive metabolite and 10-decarbamoyl 2,7-diaminomitosene (DC 2,7-DM) served as a secondary bioreductive metabolite, both of which were measured by high-performance liquid chromatography. 2,7-DM and DC 2,7-DM were produced rapidly, achieving close to their maximal concentrations at the earliest time point studied [5 min]. 2,7-DM was cleared rapidly from the tumour with apparent half-lives of 5 and 35 min after the low and high drug doses, respectively. DC 2,7-DM had a longer apparent half-life of 130 min at the higher dose but, as compared with 2,7-DM, was only a minor metabolite [the area under the curve (AUC) of 2,7-DM was 5.6-fold that of DC 2,7-DM]. At the lower drug dose, DC 2,7-DM was not detectable. Rapid formation and disappearance of bioreductive metabolites of MMC may account for the failure of previous studies to detect these products in vivo.

MeSH terms

  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Half-Life
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism*
  • Mitomycin / pharmacokinetics*
  • Mitomycin / therapeutic use
  • Mitomycins / pharmacokinetics*
  • Mitomycins / therapeutic use
  • Rats
  • Rats, Inbred Strains

Substances

  • Mitomycins
  • Mitomycin
  • 2,7-diaminomitosene