Antitumor activity and pharmacokinetics of 7-N-(p-hydroxyphenyl)mitomycin C in human tumor xenografts transplanted into nude mice.

The effects of 7-N-(p-hydroxyphenyl)mitomycin C (M-83), a derivative of mitomycin C, against eight human tumor xenografts serially transplanted into male BALB/c nude mice were evaluated. M-83 showed positive antitumor effect against six out of eight tumor strains. The antitumor spectrum of this agent was similar to that of mitomycin C except for two strains. The serum level of M-83 detected by bioassay was biphasic, elimination half-life T1/2 beta was 10.9 minutes and the area under curve AUC60(0) was 112.4 micrograms . minute/ml when 15 mg/kg of the agent was administered. In the tumor, the peak concentration and AUC60(0) detected by radioassay correlated well with the value of drug efficacy TRW/CRW. The ratio of the concentrations detected by bioassay to radioassay in the tumor was approximately 10%, which was thought to be affected by inactivation of the agent in the tumor.