[Studies on adequate intervals of cisplatin administration to ameliorate cisplatin-induced nephrotoxicity]

Experimental studies were designed in order to ameliorate cisplatin-induced nephrotoxicity. Cisplatin was injected intravenously into DS mice at a dose of 5.0 mg/kg. Plasma platinum levels declined in a biphasic fashion and were undetectable after 5 days post-infusion. Renal platinum levels decreased in the same manner as the plasma levels and revealed detectable plateau levels 5 days after single injection. Cisplatin was administer once a week for 3 consecutive weeks; serial plasma and renal platinum levels and BUN were measured 7 days after each injection. The results showed that there was no significant change in the levels of plasma platinum and BUN but that the renal platinum levels increased progressively (1.6 +/- 0.3, 3.1 +/- 0.4, 4.8 +/- 2.7 micrograms/g wet wt.). After another 6 successive weeks of cisplatin administration, 55% of mice died. The renal platinum levels and BUN of the survivors were highly increased. The renal tissue revealed histologically acute renal failure. However the renal concentration of platinum was decreased to a low level of 1.1 +/- 0.4 micrograms/g wet wt. 4 weeks after the third injection. These results suggested that cisplatin-induced nephrotoxicity could be ameliorated by adequate intervals of cisplatin administration.