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.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000378:metabolism*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C