齐多夫啶半乳糖神经酰胺脂质体在小鼠的药动学研究

Study of pharmacokinetics of AZT in mice by encapsulation in liposomes Containing galactosylceramide

目的 研究半乳糖神经酰胺脂质体包封的齐多夫啶(azidothymidine ,AZT)在小鼠体内的药动学。方法 以半乳糖神经酰胺 (galactosyceramide ,GalCer)为主要膜材制备齐多夫啶半乳糖神经酰胺脂质体 (AZT GalCer)并观察AZT Gal Cer及游离AZT在小鼠体内的药动学过程。结果 AZT GalCer组较游离AZT组血药浓度显著升高 ,特别是 30min后升高达数十倍 ;药物的Ke由 0 0 37h-1降至 0 0 2 1h-1,T1/2 由 19min延长至 35min ,AUC增加 2 .77倍。结论 齐多夫啶半乳糖神经酰胺脂质体可提高齐多夫啶的血药浓度 ,延缓药物消除速度。

AIM To study the pharmacokinetics of AZT in mice by encapsulation in liposomes Containing galactosylceramide (GalCer). METHODS AZT was encapsulated in liposomes containing GalCer and the pharmacokinetics of AZT-GalCer and free AZT were observed in mice. RESULTS Higher concentration of AZT in mice injected AZT-GalCer was found in plasma after 30 min and it was ten times as high as in mice injected with AZT. On the other hand, Ke decreased significantly from 0.037 to 0.021 h -1 , T_ 1/2 Ke increased significantly from 19 min to 35 min, and AUC was 2.77 times as high as in mice injected with AZT. CONCLUSIONS AZT-GalCer serving as a dilivery carrier could prolong the effective concentration of AZT in plasma. AZT-GalCer might have great therapeutic potential for treating AIDS.-