荷瘤小鼠静脉注射洛铂和顺铂后药物浓度的变化规律  

The concentration changes of lobaplatin and cisplatin injected intravenously in mice bearing lewis lung carcinoma

作　　者：孙明霞[1] 高献书[2] 赵玉亮[1] 秦尚彬[2] 刘朝兴[2] 张敏[2] 李晓梅[2] 

机构地区：[1]北京大学第一医院肿瘤化疗科,北京100034 [2]北京大学第一医院放射治疗科,北京100034

出　　处：《中国肿瘤临床与康复》2011年第3期212-217,共6页Chinese Journal of Clinical Oncology and Rehabilitation

摘　　要：目的研究洛铂和顺铂在小鼠血浆、肾脏和肿瘤内的药物浓度随时间变化的规律,为放疗增敏提供实验数据。方法 70只C57BL/6近交系Lewis肺癌荷瘤小鼠随机分组,按10mg药物/kg体重经尾静脉分别给小鼠注射药物(洛铂或顺铂),给药后在0.5、2、4、24、48、72、96 h分别将小鼠处死获取血液和组织标本(肿瘤和肾脏),应用ICP-MS方法测定标本铂含量。结果洛铂和顺铂的血浆药时曲线均符合三室模型,半衰期分别为51.139h和35.583h,洛铂在血浆中的清除速率大于顺铂[0.532L/(h.kg)对0.192 L/(h·kg)];洛铂和顺铂在肿瘤组织的浓度均在给药后迅速达到最大[(2.79±0.35)μg/g对(4.78±1.11)μg/g],然后迅速下降,在4 h后分别降至0.99±0.21μg/g和3.39±0.55μg/g,在96 h肿瘤中仍有药物存在,浓度分别为0.23±0.05μg/g和1.41±0.71μg/g。肿瘤药物浓度与血浆药物浓度呈对数相关,Rsq分别为0.948和0.837。结论洛铂和顺铂在小鼠体内静脉给药后半衰期长,肿瘤内药物浓度在给药后很快达到最大,在4 h降至平台期,96 h仍有药物存在,顺铂在肿瘤内的浓度高于洛铂;洛铂在小鼠体内的清除速率快于顺铂;可以通过检测血浆中的洛铂和顺铂浓度来估算肿瘤内的药物浓度。Objective To provide experimental data for radiosensitization by determining the concentration change of lobaplatin and cisplatin in plasma,tumor and kidney of mice bearing Lewis Lung Carcinoma.Methods After administering a 10mg/kg single intravenous bolus injection of either lobaplatin or cisplatin,blood and tissues（tumor and kidney） of mice were collected at the indicated time pionts（0.5,2,4,24,48,72,and 96 h）.The platinum levels were determined by inductively coupled plasma-mass spectrometry.Results The plasma concentration-time curves of both lobaplatin and cisplatin were fitted to a three-compartment model with the half life of 51.139 h and 35.583 h,respectively.Lobaplatin was cleared from the circulation more quickly than cisplatin[0.532 L/（h·kg） vs 0.192 L/（h·kg）].The concentrations of both lobaplatin and cisplatin in tumors rapidly reached the maximum（2.79±0.35 μg/g vs 4.78±1.11 μg/g）,then declined rapidly to 0.99±0.21μg/g and 3.39±0.55 μg/g at 4h,respectively.At 96h,the concentrations of both drugs in tumors were 0.23±0.05 μg/g and 1.41±0.71 μg/g,respectively.The drug concentrations in tumors were logarithmically correlated with the concentrations in plasma.Conclusion The half lifes of lobaplatin and cisplatin in mice were long.The concentrations in tumors rapidly reached the maximum and declined to a plateau at 4 h.The drugs could be detected in tumor at 96 h.The concentration of cisplatin in tumor was higher than lobaplatin.Lobaplatin was cleared from the circulation more quickly than cisplatin.

关 键 词：洛铂 顺铂 药代动力学 组织药物浓度 放疗增敏 放化疗 小鼠 

分 类 号：R965[医药卫生—药理学]