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

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.
AuthorsL Chirrey, J Cummings, G W Halbert, J F Smyth
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 35 Issue 4 Pg. 318-22 ( 1995) ISSN: 0344-5704 [Print] Germany
PMID7828274 (Publication Type: Journal Article)
Chemical References
  • Mitomycins
  • Mitomycin
  • 2,7-diaminomitosene
Topics
  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Half-Life
  • Mammary Neoplasms, Experimental (drug therapy, metabolism)
  • Mitomycin (pharmacokinetics, therapeutic use)
  • Mitomycins (pharmacokinetics, therapeutic use)
  • Rats
  • Rats, Inbred Strains

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