EXPERIMENTAL STUDIES ON THE PHARMACOKINETICS AND NEPHROTOXICITY OF CARBOPLATIN (CIS-DIAMMINE-1, 1-CYCLOBUTANE DICARBOXYLATE PLATINUM II) IN RATS

Abstract

To study the nephrotoxicity of carboplatin (cis-diammine-1, 1-cyclobutane dicarboxylate platinum II, CBDCA), an analogue of cisplatin, we examined its pharmacokinetics and functional and histopathological changes of the kidney in rats that received i.v. injection of carboplatin. Platinum concentrations in the whole plasma rapidly decreased during the first 2 hours and was undetectable at 72 hours following the carboplatin administration. Approximately 90% of the platinum in the whole plasma was ultrafilterable during the first 30 minutes. The renal tissue concentrations of platinum rapidly decayed during the first 4 hours and then slowly declined up to 120 hours following the carboplatin administration. Platinum concentrations in the renal cortex showed higher levels than those in the renal medulla throughout the experimental period. BUN levels were within the normal range except on day 7. Serum creatinine levels remained stable and normal during the 7 days. Histopathological alterations of the renal tubules were not observed during the experimental period. These results suggest that carboplatin has less nephrotoxicity than cisplatin, because of its rapid excretion through glomerulus and less accumulation in the tubular cells.