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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 determine the content of cisplatin (DDP) in plasma by high performance liquid chromatography (HPLC) and to study the pharmacokinetics and pharmacokinetic parameters of cisplatin-loaded magnetic nanocapsules in rabbits. Methods Twelve rabbits were randomly divided into 2 groups. DDP cisplatin magnetic nanoparticles and DDP were intravenously injected into rabbits’ ears at a dose of 3 mg.kg-1 (DDP level) respectively. Blood samples were collected from the contralateral ear artery at the set time and the plasma DDP concentration was determined by modified HPLC. Pharmacokinetic analysis of plasma drug concentration-time data was performed using the 3P97 pharmacokinetic program. Results The single dose intravenous injection of DDP in rabbits pharmacokinetic characteristics in line with two-compartment model, carrying cisplatin magnetic nano-drug is in line with the three-compartment model. The main kinetic parameters of cisplatin magnetic nanoparticle scavenging rate (CL) was 0.620 times that of DDP, t1 / 2α was 1.579 times of DDP, t1 / 2β was 0.552 times of DDP, Vd was 1.845 of DDP Fold, plasma concentration - area under the curve of time (AUC) is 1.237 times DDP. Conclusions The experimental results show that the magnetic nanoparticles containing cisplatin modified to improve the stability of the drug, and cisplatin magnetic nano-drug to change the pharmacokinetics of DDP. Pharmacokinetic parameters indicate that the drug is excreted from the body through bioconversion or excretion and the tissue uptake of the drug is increased.