紫衫醇注射液及其脂质体在大鼠体内的相关药动学参数比较

The pharmacokinetic comparison of paclitaxel injection and paclitaxel liposome in rats

目的比较紫杉醇脂质体与紫杉醇注射液在大鼠体内的血药浓度及相关药动学参数。方法大鼠经尾静脉注射紫杉醇注射液或紫杉醇脂质体注射液12mg／kg后，采用HPLC法测定大鼠体内的血药浓度，得出药一时曲线图及相关药动学参数，并采用SPSS13．0统计软件将血药浓度进行配对t检验。结果在大鼠体内，紫杉醇及其脂质体在血浆样品中的浓度分别为（0．18±0．07）c／（mg·L）、（50±9．2）C／（mg·L），差异有统计学意义（t=5．879，P〈0．01）；紫杉醇脂质体药时曲线下面积（AUC）较紫杉醇注射液大（17．693±2．657VS10．812±2．846，t=4．892，P〈0．01），表观分布容积（Vc）较紫杉醇注射液小[（1．629±4．91）X10～Lvs（5．268±1．121）×10～L，t=3．75，P〈0．01]，清除率C1（s）较紫杉醇注射液慢[（7．2±1．0）×10^-4 LVS（1．2±2．7）×10^-4 L，t=4．25，P〈0．01]。结论紫杉醇脂质体与紫杉醇注射液在大鼠体内药动学有显著不同，脂质体制剂具有长效和缓释的特点，在维持较长的体内循环时间的同时，能够更好地浓聚于靶组织，减少药物对其他组织的毒副作用并增加疗效。

Objective To compare the differences of pharmacokinetic parameters of paclitaxel injections and liposome. Methods An high performance liquid chromatography （HPLC） assay method was established to estimate the blood concentrations of paclitaxel after caudal vein administration of 12 mg/kg weigh. The blood concentration-time curves as well as correlated pharmaciokinetic parameters were obtained. Moreover, the data were analyzed with t-test. Results In rats, the mean drug concentration in plasma of paclitaxel injection and paclitaxel liposome were （ 0. 18 ± 0. 07 ） C/（ mg . L） and （ 50 ± 9. 2 ） C/（ mg. L）, respectively, and there were significant differences between the two formulations （ t =5. 879, P 〈0. 01 ） ; compared with paclitaxel injection, the area under concentration-time curve （AUC） was bigger （17. 693 ± 2. 657 vs 10. 812 ~2. 846, t =4. 892, P 〈0. 01）, the apparent volume of distribution（Vc） was smaller [ （1. 629 ±4. 91 ） x 10-3 L vs （5. 268 ± 1. 121 ）x 10-3 L, t =3.75, P 〈0.01 ], the clearance rate（C1） was slower [ （7. 2 ± 1.0） x 10 -4 L vs （ 1.2 ± 2. 7） x10 -4 L, t = 4. 25, P 〈 0. 01 ], in the paclitaxel liposome. Conclusions Paclitaxel liposome has higher efficacy, longer release time, higher target tissue concentration, and lower side effects than paclitaxel injection.