DISPOSITION AND METABOLISM OF KW-2149, A NOVEL ANTICANCER AGENT

KW-2149 is a new derivative of mitomycin C (MMC). The plasma concentra tions, distribution, metabolism, and excretion of [H-3]-KW-2149 in nor mal and tumor-bearing mice after i. v. administration of 16.6 mg/kg we re investigated. The plasma radioactivity decreased biexponentially af ter i. v. administration in normal mice. However, the unchanged drug d isappeared rapidly, showing a half-life (t1/2) Of 9.7 min, which was s horter than MMC's (18 min). The radioactivity was excreted in mouse ur ine (33%) and feces (58%) within 144 h. High radioactivity was distrib uted in the gallbladder, liver, kidney, pancreas, and lung at 1 h afte r i. v. administration to normal mice. The tumor concentration was low er than the plasma or blood concentration. The lowest radioactivity wa s observed in the brain. The metabolic rate of KW-2149 was very rapid. The methyl sulfide form (M-16), the symmetrical disulfide dimer (M-18 ), and the albumin conjugate were detected in plasma, which possessed anticellular activity. The specific anticellular activity of these com pounds against uterine carcinoma (HeLa S3) was 1/100, 1, and 1/20 resp ectively, as compared with that of KW-2149.