吐温80对9-硝基喜树碱脂质体药物动力学性质的影响

Effect of Tween80 on the Pharmacokinetics of 9-nitrocamptothecin Liposome

目的:考察吐温80对9-硝基喜树碱(9-NC)脂质体体内药物动力学以及内酯型/羧酸盐型平衡的影响。方法:采用薄膜法制备9-NC脂质体以及吐温80修饰的9-NC脂质体;12只大鼠随机分为两组,按1.5 mg.kg-1剂量分别给予9-NC普通脂质体和吐温80修饰的脂质体,于不同时间点取血,处理后测定9-NC内酯型浓度和总浓度(内酯/羧酸盐)。采用统计矩模型利用3P97程序计算药物动力学参数。结果:采用表面活性剂吐温80进行修饰后,9-NC内酯型和总浓度的AUC分别提高了1.47倍和1.65倍,内酯型和总浓度的清除率CL和表观分布容积Vss显著下降(P<0.01)。此外,总浓度的MRT以及t1/2延长(P<0.05)。结论:吐温80修饰使得9-NC内酯型比例有所下降,但没有显著性差异,9-NC吐温修饰对9-NC脂质体具有一定的长循环效果。

Objective： To study the effect of tween 80 on the pharmacokinetics and lactone-carboxylate forms＇ banlance of 9-nitrocamptothecin（9-NC） liposome.Method： 9-NC liposome and 9-NC liposome modified by tween 80 were made by forming membrane.Twelve rats were divided into two groups,they were injected by 9-NC liposome and 9-NC liposome modified by tween 80 in dose of 1.5 mg·kg-1.Blood samples were collected at different times after injecting.The concentrations of lactone form and total drug of 9-NC were determined after modification.Pharmacokinetic parameters were calculated in 3P97 program by statistical moment.Results： With modification by tween 80,the AUC values of lactone form and total drug of 9-NC were increased 1.47 and 1.65 times,their CL and Vss decreased notably（P0.01）.Conclusion： The proportion of lactone form decrease,but the difference is not notable after modified by tween 80.Modification of tween 80 produce some effects of long cycle on 9-NC liposome.