载顺铂磁性纳米药物药动学研究

Pharmacokinetic Study of Modified Cisplatin Magnetic Nanomedicine

目的高效液相色谱法(HPLC)测定血浆中顺铂(DDP)含量,研究载顺铂磁性纳米药物在家兔体内的药动学特征及其相关药动学参数。方法家兔12只,随机分为2组。分别于兔耳缘静脉注射3 mg.kg-1(按DDP含量计)剂量载顺铂磁性纳米药物和DDP,按设定时间于对侧耳缘动脉采血,通过改良HPLC法测定血浆中DDP浓度。以3P97药动学程序处理血浆药物浓度-时间数据,进行药动学分析。结果本实验单剂量静注DDP在家兔体内的药动学特征符合二室模型,载顺铂磁性纳米药物则符合三室模型。主要动力学参数与DDP相比,载顺铂磁性纳米药物的清除率(CL)是DDP的0.620倍,t1/2α是DDP的1.579倍,t1/2β是DDP的0.552倍,Vd是DDP的1.845倍,血药浓度-时间曲线下面积(AUC)是DDP的1.237倍。结论实验结果表明,载顺铂磁性纳米药物经改良,提高了药物的稳定性,载顺铂磁性纳米药物改变了DDP的药动学特性。药动学参数表明,药物通过生物转化或排泄从体内消除加快,组织对药物的摄取量增加。

OBJECTIVE To explore the pharmacokinetic characteristics and assess the safety of modified cisplatin（DDP） magnetic nano medicine. METHODS Twelve New Zealand rabbits were divided into 2 groups at random. DDP and magnetic nanomedi- eine （DDPmtnm） of 3 mg·kg-1 was administered by the vein of auris edge. The plasma eoneentration of DDP was detected by High Performance Liquid Chromatography （HPLC）. The detedted DDP concentration in plasma was analyzed by 3P97 software. RESULTS The pharmacokinetics of DDP was best described by a twocompartment model,whereas the DDP mtnm＇s was described by a threecompartment model. As for the pharmacokinetic parameters,the clearance from blood, the distribution half life （t1/2a） , the elimination half life （t1/2β） , the apparent distribution volume （ Vd ） and the area under curve （AUC） of DDPmtnm was 0. 620, 1. 579,0. 522, 1. 845, and 1. 237 times of those of DDP, respectively. CONCLUSION The results show that the stability of the modified DDPmtnm is enhanced and the distribution characteristics of DDP in vivo is changed. The pharmacokinetic parameters of DDPmtnm indicate that the elimination of the drug from the body by biotransformation or excretion become much quicker and the uptake of the drug by the tis- sues increase as well.