Distribution and excretion of 7-N-(p-hydroxyphenyl)-mitomycin C in normal mice

Tissue distribution, excretion and stability of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) in normal mice were compared with those of mitomycin C (MMC) by microbiological assay. M-83 was more rapidly inactivated by mouse liver homogenate in vitro than MMC. MMC could not be detected by thin-layer chromatography-bioautography in the reaction mixture of M-83 incubated with mouse liver homogenate, or in the mouse urine. Both M-83 and MMC exhibited biphasic serum elimination characteristics after iv bolus injection. When these compounds were administered at their approximate LD50 (M-83, 20 mg/kg; MMC, 8 mg/kg) iv into mice, their half-lives were 17.9 and 19.8 min, respectively. However, the half-life of M-83 (10.2 mg/kg) after iv bolus injection was 7.5 min and was shorter than that of MMC (8 mg/kg) at the molar equivalent dose. In ip administration of an approximate LD50, M-83 and MMC exhibited similar drug absorption and elimination patterns. When both compounds were administered iv at the approximate LD50, the 24-hr urinary recoveries of unchanged M-83 and MMC were 2.85 and 19.26%, respectively. The distribution of M-83 in various tissues was similar to that of MMC.