半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药物动力学研究(英文)

Pharmacokinetic analysis of galactosylated albumin magnetive Adriamycin nanoparticle(GAMAN) in home rabbits

目的对家兔一次性颈静脉给药,检测自制药物与普通阿霉素在药动力学方面有无差异及了解新药的药动学特点。方法家兔12只,随机分为两组,每组6只,均予颈静脉置管、注射、抽血,一组按3.0mg/kg给予阿霉素;一组按63.2mg/kg给予半乳糖化白蛋白磁性阿霉素纳米粒,每次抽血1ml,分离血清低温保存,以氯仿-甲醇液萃取阿霉素,在高效液相色谱仪下检测色谱峰高。根据阿霉素标准曲线求血清中阿霉素浓度。以“3P87”进行药动学分析。结果阿霉素与半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药动学规律符合三室开放模型;与阿霉素相比,实验组药物的消除相半衰期延长了1.9～3.2倍,清除率是阿霉素的0.5369倍;血药浓度-时间曲线下面积(AUC)是阿霉素的1.3697倍。结论阿霉素经过与白蛋白、磁性微粒结合,并以半乳糖修饰,改变了原药的体内分布特性,延长了药物半衰期,增加了靶器官肝脏的药物浓度。

Objective: Through one-off jugular vein injection on home rabbits with different two drugs, to check up whether the pharmacokinetic of galactosylated albumin magnetive Adriamycin nanoparticle(GAMAN) was different to the Adriamycin, and to find out the pharmacokinetic characteristics of the GAMAN. Methods: The twelve home rabbits were divided into two groups in random six in each. Every rabbit was put a pipe in its jugular vein, then injected drugs and phlebotomized. One group was given Adriamycin 3 mg/kg to every rabbit, the other group was given GAMAN 63.2 mg/kg equivalent to Adriamycin 3 mg/kg to every rabbit. Phlebotomized 1 ml each time, then separated serum and saved 0.3 ml at low temperature, extracted the Adriamycin with chloroform-carbinol, put it under the High Performance Liquid Chromatography (HPLC) to examine the special chromatogram peak value ratio. Finally, the concentration of the Adriamycin in serum was accounted according to the standard curve of the Adriamycin. Then pharmacokinetic parameter was analyzed in 3P87 software. Results: The pharmacokinetic of Adriamycin and GAMAN in home rabbits were according with the three chamber open models. Compared to Adriamycin, the half life of GAMAN was prolonged from about 1.9 to 3.2 times; the clearness of GAMAN from blood was 0.5369 times to Adriamycin; and the Area of Under the Curve(AUC) was 1.3697 times to Adriamycin. Conclusion: After combined with albumin and magnetic particulates, and embellished with galactosylate, GAMAN has a different distribution compared with Adriamycin; and has a longer half life; Suctioned by the magnet at the right up quadrant, GAMAN can be assembed to a higher concentration at targeted organ liver.