奈达铂(Nedaplatin)在大鼠体内的肾毒性和骨髓抑制的时辰毒理学研究  

Medication Time Involved in Nedaplatin-induced Nephrotoxicity and Myelosuppression in the Rats

作　　者：崔一民[1] 孙忠民[1] 杉本孝一 藤村昭夫 

机构地区：[1]北京大学第一医院药剂科,北京市100034 [2]自治医科大学临床药理学教室

出　　处：《中国医院用药评价与分析》2004年第2期106-109,共4页Evaluation and Analysis of Drug-use in Hospitals of China

摘　　要：目的 :以大鼠为实验对象 ,通过测定给药时间与奈达铂 (Nedaplatin)诱发的肾毒性和骨髓抑制的关系 ,研究铂 (Pt)衍生物奈达铂的时辰毒理。方法 :于 8:0 0或 2 0 :0 0通过尾静脉给S-D大鼠 (n =8)注射奈达铂 (5mg kg体重 )或空白溶媒 ,给药间隔为 7天。定期采血、采尿测定血清肌苷清除率和周边血中的中性粒细胞。最后一次给药后 2 4小时 ,处死动物 ,采集肾脏和大腿骨用于Pt浓度测定和组织学检查。共给药 6次。结果 :2 0 :0 0给药组的体重抑制明显高于 8:0 0给药组 ,实验结束时 ,两实验组均有2只动物死亡。奈达铂诱发的骨髓抑制没有明显的给药时间相关性 ,但 2 0 :0 0给药组的肾毒性明显大于 8:0 0给药组。肌苷清除率和肾组织损伤积分均与肾皮质中Pt的含量有很好的相关性。结论 :奈达铂诱发的肾毒性和药物在组织中的蓄积与给药时间有很好的相关性 。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.

关 键 词：奈达铂 大鼠 肾毒性 骨髓抑制 时辰毒理学 给药时间 

分 类 号：R692[医药卫生—泌尿科学] R733.3[医药卫生—外科学]