Pharmacokinetics of cis-diammine (glycolato) platinum (254-S), a new platinum antitumor agent, following an intravenous and intraperitoneal infusion bioactive platinum concentration profile

The pharmacokinetics of cis-diammine (glycolato) platinum (254-S) was investigated in cancer patients following intravenous and intraperitoneal infusion. The serum concentrations of total and unbound 254-S were determined by bioassay and chemical assay as platinum. Platinum detected by bioassay was thought to be active and unchanged 254-S. Almost all of platinum in plasma were found to be active and unbound to protein because of no differences in the concentrations determined by bioassay and chemical assay and in plasma and plasma filtrate. In abdominal ascites, platinum concentrations determined by bioassay corresponded with those determined by chemical assay, suggesting that 254-S was stable in abdominal ascites. The Cmax and AUC of active 254-S in plasma determined by bioassay following an intraperitoneal infusion were about 60% and 60-80% of those following an intravenous infusion, respectively. These results showed that 254-S was well absorbed into systemic circulation from abdominal ascites as an active form. It is concluded that antitumor effect may be obtained following an intraperitoneal infusion of 254-S as well as for the reduction of abdominal ascites.