[Experimental study on carboplatin toxicity--a comparison with cisplatin].
The toxic potencies of cisplatin and carboplatin were compared in male Wistar rats. The tissue concentration of platinum in rats was 5- to 13-fold larger with cisplatin treated group than carboplatin treated one. The histopathologic examination of various organs revealed severe myelosuppression and mild toxicity in the kidney, testis, spleen and intestine of rats treated with carboplatin. The toxicity of carboplatin was milder than cisplatin in all organs except bone marrow. This reduced toxicity of carboplatin can be accounted for by the presence of a stable dicarboxylate chelate ring structure of this drug, resulting in a much slower rate of hydrolysis to the active form, and the differences in nuclear protein phosphorylation between normal cells and tumor cells. The decreased nephrotoxicity of carboplatin may be due in part to lower drug accumulation in the renal tubular epithelium via the basement transport mechanism.
Suzuki
K
K
Dept. of Urology, Yaizu Municipal Hospital.
Usami
T
T
Sudoko
H
H
Ohtawara
Y
Y
Tajima
A
A
Kawabe
K
K
Aso
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D016190:Carboplatin; D002945:Cisplatin / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D004848:Epithelium / Q000378:metabolism; D006868:Hydrolysis; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin