Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model

Cis-Dichlorodiammineplatinum (CPDD) NSC 119875 was given at toxic doses (3 mg/kg) to three groups of dogs. The renal toxicity was avoided with massive prehydration and with mannitol induced diuresis. The bone marrow toxicity was unaltered by either manipulation. The data presented indicate that a better therapeutic index has been achieved by osmotic diuresis with mannitol. Blood levels and urine levels measurements show that the pharmacokinetics of the drug are unaltered, the urinary concentration of drug being low in the first few hours, but with similar urinary drug recovery in all three groups.