Studies on Nephrotoxicity Following a Single and Repeated Administration of cis-Diamminedichloroplatinum (CDDP) in Rats

MIZUSHIMA, Y., NAGAHAMA, H., YOKOYAMA, A., MORIKAGE, T. and YANO, S. Studies on Nephrotoxicity Following a Single and Repeated Administration of cis-Diamminedichloroplatinum (CDDP) in Rats. Tohoku J. exp. Med., 1987, 151 (2), 129-135-Nephrotoxicity following a single and repeated administration of cis-diamminedichloroplatinum (CDDP) was investigated in male Wistar rats. When CDDP in a single dose of 4mg/kg was injected i.p, into animals, serum creatinine (Cr) and blood urea nitrogen (BUN) reached a peak after 4 days and returned to the initial levels within two weeks. Nephrotoxicity of CDDP was dose-dependent, and related to the route of administration in the following order of i.p.s.c.i.v. When CDDP (4mg/kg) was injected i.p. repeatedly at intervals of three weeks, a decrease in nephrotoxicity was observed after the 2nd injection of drug. This decreased nephrotoxicity was detected as early as a week after the 1st injection. Following the 3rd injection, nephrotoxicity showed an accumulative pattern. The change in the route of administration or its regimen did not alter the pattern of CDDP-induced nephrotoxicity. Decreased nephrotoxicity after the 2nd injection of the drug seems to be interesting from viewpoint of a host defense response.