Mechanisms for the renal secretion of cisplatin.

Cisplatin (cisDDP) inhibits the active uptake of tetraethylammonium and p-aminohippurate by mouse kidney slices. The shapes of the dose-response curves for inhibition of the organic cation and organic anion transport are different, and the inhibition is competitive in each case. Thus, the inhibition by cisDDP may be due to interaction of cisDDP or its aquated products with the specific transport sites rather than to nonspecific metabolic poisoning of the slices by cisDDP. In mice, cimetidine inhibits the renal secretion of tetraethylammonium but fails to inhibit the secretion of p-amminohippurate. The renal clearance of total platinum in mice treated with cisDDP did not exceed that of inulin; however, the clearance of platinum was reduced by cimetidine. These results suggest that the organic cation secretory system plays a role in the renal handling of cisDDP or its products.