Tetraplatin (tetrachloro[d,l-trans]1,2-diaminocyclohexane
platinum IV (
TTP)) is a new
platinum analogue active against L1210 murine
leukemia that is resistant to
cisplatin (diamminedichloroplatinum II (DDP)). Since nephrotoxicity is a significant problem with DDP
therapy, we compared the effects of equitherapeutic doses of
TTP and DDP on renal structure and function in rats. We also studied the effects of the 2
platinum compounds on the distribution and excretion of
gentamicin (GENT), an
antibiotic that is excreted solely by the kidneys. Rats treated intravenously with 2.85 mg/kg of DDP on days 1, 5 and 9 had significantly different plasma
urea nitrogen (BUN) levels and
creatinine clearance rates on day 16 than those given the same doses of
TTP. The renal function of
TTP-treated rats did not differ from that of controls or rats given only GENT. Twenty-four hours after a single GENT dose (given on day 15), DDP-treated rats had higher GENT concentrations in the plasma, liver and spleen than rats given GENT alone.
TTP-treated rats had higher GENT levels only in the spleen. DDP-treated rats retained a higher percentage of the injected
platinum in the renal cortex than those treated with
TTP. Light microscopic examination of renal tissue showed necrotic cells and dilated tubules in the proximal tubules of DDP-treated rats while the kidneys of
TTP-treated rats were largely indistinguishable from those of controls. Thus, our results indicate that the distribution of
platinum in the kidneys differs between rats treated with
TTP and those treated with DDP. This may partly explain the considerably lower nephrotoxicity of
TTP.