[Pharmacokinetics of mitomycin C and its derivative (KW-2083)].
Pharmacokinetics of MMC was studied by bioassay method in cancer patients and experimental animals, and they were compared with those of a new mitomycin derivative, KW-2083. The blood level of MMC decreased relative by rapidly, t 1/2 beta in iv dose of 30, 20 and 10 mg/body to man was 50, 41 and 33 minutes, respectively. The drug level was able to increase locally by employing perfusion, arterial infusion, hemi-upper body infusion and intra-cavitary injection. The tissue level of MMC was high in the lung, kidney, muscle and skin, and moderate in the tumor of S180 bearing mice. MMC was inactivated strongly in the homogenates of the liver and kidney, and moderately in the heart and intestine of human tissues. The inactivation was enhanced by the addition of NADPH, vitamin B6, glutathione, etc. The blood level of KW-2083 in patients and mice decreased more rapidly than MMC. T 1/2 beta of KW-2083 in patients after iv injection at 70, 40 and 20 mg/body was about 18 minutes. The tissue level of KW-2083 in S 180 bearing mice was the highest in the lung and skin, followed by the kidney and tumor. The elimination rate of the drug from each tissue was more rapid than that of MMC. KW-2083 was highly excreted into the bile and more highly inactivated in the homogenates of the liver, kidney, muscle, etc. as compared with MMC. These pharmacokinetic behaviours of KW-2083 might be related to the lower toxicity and higher therapeutic ratio in experimental animals.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; C027281:7-N-(4-hydroxyphenyl)mitomycin C