OBJECTIVE : To determine a chronotoxicological property of Nedaplatin, a platinum derivative, we examined medication time
dependent
nephrotoxicity and
myelosuppression induced by nedaplatin in the rats. METHODS : Nedaplatin (5 mg/kg body weight) or blank dissolvant was injected intravenously to male Sprague-Dawley rats (n=8 in each group) at 8:00 or 20:00 every 7 days. Blood and urine samples were collected periodically to measure creatinine clearance (CLcr) and neutrophil count in peripheral blood. After last medication , kidneys and femoral bones were obtained for analyzing platinum concentration and histopathology. Nedaplatin was totally given 6 times.RESULTS: Suppression of body weight gain by nedaplatin was significantly greater in 20:00 than that in 8:00 group. 2 rats died in each group during nedaplatin treatment. Nedaplatin did not show apparent medication dependent myelosuppression. Nephrotoxicity was higher in 20:00 group. The changes in CLcr and the scores of renal histopathology were well correlated with the platinum contents in the renal cortex. CONCLUSION: Nedaplatin-induced nephrotoxicity and drug accumulation in the tissues are well correlated with medication time , so it must be paid attention to medication time when this kind of drugs are used in the clinic.