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

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。

Degradation kinetics of azidothymidine palmitate in different homogenate of mice

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..