A comparison of the effects of tetraplatin and cisplatin on renal function and gentamicin pharmacology in rats.
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.
Engineer
M S
MS
Department of Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Brown
N S
NS
Ho
D H
DH
Newman
R A
RA
Bulger
R E
RE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005839:Gentamicins / Q000493:pharmacokinetics* / Q000494:pharmacology; D007668:Kidney / Q000032:analysis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000032:analysis; D008297:Male; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010984:Platinum / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000032:analysis
D000970:Antineoplastic Agents; D005839:Gentamicins; D009944:Organoplatinum Compounds; D010984:Platinum; D002945:Cisplatin; C049777:ormaplatin