The comparative tissues distribution of platinum and 14C in mice receiving 14C-labelled carboplatin

Since the reactivity of carboplatin depends on the rate of removal of the 1,1-cyclobutanedicarboxylate ligand, the time course of this dissociation has been determined in various tissue and body fluids using 14C-labelled carboplatin (cis-diammine[1,1-cyclobutane-1-14C-dicarboxylate]platinum II). Mice received 14C-carboplatin (80 mg/kg; 1.1 mCi/kg, i.v.), and tissue was removed at times ranging from 5 min to 5 days posttreatment. Following solubilization, tissue aliquots were analyzed for platinum and 14C contents. Carboplatin remained intact for up to 2 h posttreatment, since the ratio of 14C: Pt in tissues (nmol/g) was unity. Thereafter, the 14C ligand was released from the molecule and preferentially removed from tissues, indicated by decreasing 14C: Pt ratios. The elimination half-lives for Pt varied between tissues (40-156 h). In contrast, the corresponding half-lives for the 14C species were similar in most types of tissue (18-35 h), although those in the liver and spleen were exceptional (210 and 90 h, respectively). At 5 days a maximum of 4%-24% of the total Pt in tissue might exist as intact drug. Thus, the metabolic handling of carboplatin varies according to the tissue, since the elimination of the 14C cyclobutane dicarboxylate species from most tissue was similar and Pt elimination was slower and tissue-dependent.