紫杉醇脂质体大鼠体内药动学考察

Study on Pharmacokinetics of Paclitaxel Liposome in rats

目的使用HPLCUV法测定大鼠体内紫杉醇血药浓度,考察紫杉醇脂质体在大鼠体内药动学。方法大鼠尾静脉注射紫杉醇脂质体及紫杉醇注射液,血浆用叔丁基甲醚提取。ODS柱,流动相为甲醇水(65∶35),检测波长227nm。结果本法在0.05～50μg·ml-1范围内线性良好,日内、日间精密度RSD<6%,高、中、低3个浓度下提取回收率均大于90%。紫杉醇脂质体及紫杉醇注射液血药浓度经时曲线均符合二室模型。t1/2β分别为(11.19±0.08)h和(7.49±0.80)h,AUC分别为2615.89±770.58(mg·L-1·min-1)和904.94±25.36(mg·L-1·min-1)。结论与市售紫杉醇注射液相比,紫杉醇纳米脂质体有一定的长循环作用,且提高大鼠体内的利用度。

AIM To study the phannacokinetics of paelitaxel liposome in rats. METHODS Plasma was extracted with tea-butyl methyl ether and norethisterone was employed as internal standard after iv. paclitaxel liposome and taxol injection in rats. Plasma samples were analyzedon a C18 columnat227 nm and the mobile phase was methanol and water （ 65 ： 35 , v / v ） . RESULTS Linearity was confirmed over the whole calibration range from 0.05μg/ml to 50μg/ml（ r = 0.9999 ）. The intra- and inter-day precisions （RSD） of analysis were lower than 6% and the extraction recovery at three different concentration were better than 90%. The plasma concentration-time profile in rat after iv injection of paclitaxel liposome or taxol injection follow a bi-exponential disposition. T1/2β are （11.19 ±0.08） h and （7.49 ± 0.80） h, A UC are 2615.89±770.58（mg·L^-1·min^-1） and 904.94±25.36 （mg·L^-1·min^-1） respectively. CONCLUSION Paclitaxel liposome hasa long-circulating action and improve bioavailahilty of paclitaxle in rat to some extent in comparison with conventional taxol injection.