Increased tissue deposition and decreased excretion of platinum following administration of cisplatin to cisplatin-pretreated animals

Abstract

Guinea pigs were pretreated IP with cisplatin (10 mg/kg) for various times before IV administration of 195mPt-labeled cisplatin. Concentrations of 195mplatinum were greater in tissues of pretreated animals than in those of control animals. Amounts of 195mplatinum in subcellular fractions from pretreated rabbits were similarly greater in pretreated animals. Amounts of radioactivity appeared to be greatest in animals receiving a larger number of pretreatment injections, even though the total amount of cisplatin administered was equal in all groups. BUN was elevated on day 1 after the radioactive dose only in those animals which had been pretreated. Urinary excretion of platinum was significantly less in pretreated than in control animals. It appears that pretreatment with cisplatin damages the kidney severely enough for subsequent doses of cisplatin not to be excreted as efficiently, thus leading to a greater tissue deposition of platinum in pretreated animals.