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.
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Authors | L Chirrey, J Cummings, G W Halbert, J F Smyth |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 35
Issue 4
Pg. 318-22
( 1995)
ISSN: 0344-5704 [Print] Germany |
PMID | 7828274
(Publication Type: Journal Article)
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Chemical References |
- Mitomycins
- Mitomycin
- 2,7-diaminomitosene
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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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