Pharmacokinetics of new cisplatin analogues in experimental animals

: An equi-toxic dose of CDDP and its analogues (254-S, NK-121, CBDCA and DWA-2114 R) was administered to rabbits and S.180 bearing mice, and the pharmacokinetics were studied. Blood levels: Plasma total platinum (Pt) curves of 5 drugs decreased, showing a biphasic function. The shortest t 1/2 alpha and the longest t 1/2 beta were observed in CDDP group, which correlated with the rate of protein binding (CDDP greater than DWA-2114R greater than NK-121 greater than CBDCA greater than 254-S). Tissue distribution: The tissue levels of Pt decreased slowly, and showed a similar pattern among 5 drugs. The highest level was observed in the kidney, liver and skin, with a moderate high level in the tumor, lung, spleen and thymus, followed by the heart, pancreas, stomach, intestine, muscle and testis in that order. The lowest level was in the brain in S.180 bearing mice.