Effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of mitomycin-C in the rat.

The effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of intravenously-administered mitomycin-C have been studied in the Wistar-Furth rat. Five test animals received total body irradiation (1000 rads) followed by intravenous administration of 3 X 10(8) bone marrow cells per kg body weight. Five control animals were sham-irradiated and received an equal volume of blank suspension medium. One day after these treatments, each rat received mitomycin-C (10 mg/kg) by rapid intravenous injection and serial blood samples were obtained. Serum mitomycin-C concentrations were measured by high performance liquid chromatography and pharmcokinetic parameters were calculated after NONLIN analysis of data. Smaller total body clearances in test animals were probably due to radiation-induced inhibition of microsomal enzyme activity. Reduced volumes of distribution were observed in test animals although the reason for this is unclear. Future studies should assess the clinical significance of these results.