吐温80对9-硝基喜树碱脂质体药物动力学性质的影响

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。

Effect of Tween80 on the Pharmacokinetics of 9-nitrocamptothecin Liposome

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 V_ss decreased notably(P<0.01). 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.