齐多夫定棕榈酸酯及其脂质体在小鼠各组织中的降解动力学  

Degradation kinetics of azidothymidine palmitate in different homogenate of mice

作　　者：周欣羽[1] 王艳芝[2] 魏守刚 邓意辉[1] 王宁[1] 赵静[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]郑州大学药学院,河南郑州450001 [3]阿斯利康贸易有限公司,辽宁沈阳110001

出　　处：《沈阳药科大学学报》2008年第1期6-9,共4页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(30371694)

摘　　要：目的考察齐多夫定棕榈酸酯及其脂质体在小鼠各组织中的降解动力学。方法将齐多夫定棕榈酸酯溶液、齐多夫定棕榈酸酯脂质体分别与小鼠各组织匀浆混合,37℃恒温孵育后,采用HPLC法测定齐多夫定棕榈酸酯浓度。结果齐多夫定棕榈酸酯在小鼠心、肝、脾、肺、肾、脑中的表观降解速率常数(kobs,min-1)依次为:7.5×10-3、5.43×10-2、9.8×10-3、9.9×10-3、2.48×10-2、6.4×10-3。经脂质体包裹的齐多夫定棕榈酸酯在小鼠心、肝、脾、肺、肾、脑组织匀浆中的表观降解速率常数(kobs,min-1)依次为:1.18×10-3、6.70×10-3、1.20×10-3、1.70×10-3、3.00×10-3和1.10×10-3。结论齐多夫定棕榈酸酯及其脂质体在小鼠各组织匀浆中的降解速率不同。经脂质体包裹后,齐多夫定棕榈酸酯在小鼠各组织匀浆中的降解速率降低,表明脂质体对其具有较好的保护作用。Objective To investigate the degradation pharmacokinetics of azidothymidine palmitate and azidothymidine palmitate liposomes in different homogenate of mice. Methods Azidothymidine palmitate liposomes were prepared by the ipv-alcohol-injection method. Solution of azidothymidine palmitate and azidothymidine palmitate liposomes were incubated with different homogenate of mice at 37 ℃ and then HPLC was used to determine the concentration of azidothymidine palmitate. Results The apparent rate constants （kobs, min^-1） of azidothymidine palmitate in different homogenate of mice were as the follows： 7.5 × 10^-3,5.43 × 10^-2, 9.8 × 10^-3, 9.9 × 10^-3, 2.48 × 10^-2, 6.4 × 10^-3. After entrapped by liposome, the Kobs （min^-1） changed to the following： 1.18×10^-3, 6.70 × 10^-3, 1.20 × 10^-3,1.70 × 10^-3,3.00 × 10^-3 and 1.10 × 10^-3. Conclusions Degradation rate constants of azidothymidine palmitate and azidothymidine palmitate liposomes in different homogenate of mice are different. After entrapped into liposome, the constants lower, which indicates that liposome has good protective effect on azidothymidine palmitate.

关 键 词：齐多夫定棕榈酸酯 组织降解 药物动力学 脂质体 高效液相色谱法 

分 类 号：R94[医药卫生—药剂学]