Pharmacokinetics of therapeutic doses of isotopically labeled platinum antitumor agents in the mouse and rat.

The pharmacokinetics of the antitumor agents ethylenediamine platinum dichloride and cisplatin have been investigated in mice bearing the ADJ/PC6 plasma cell tumor after therapeutic doses of these agents, labeled either with 191Pt or in the ligand with 14C. The distribution of the radioactive labels has been estimated in tumor, kidney, liver, and intestine in treated animals from 1 hour to 15 days after administration. The two labels, on ligand and on Pt, were equivalent only in some cases with respect to the total radioactivity within a tissue. Patterns of isotope distribution varied with time and tissue and suggested that the metal-ligand bond was dissociated as early as 1 hour after administration.