紫杉醇脂质体在大鼠体内的药动学

Pharmacokinetics of Taxol-liposome in Rat

建立了大鼠血中紫杉醇ＨＰＬＣ检测法。血样用乙醚提取后在Ｃ１８柱上以甲醇-水-乙腈（４∶３∶３）为流动相，检测波长为２２７ nm，炔诺酮为内标条件下检测。线性范围为0.1～120.0 μg/ml，最低检测限为2.5 μg，萃取回收率大于80.0％，日内及日间ＲＳＤ皆小于3.0％。用本法对大鼠iv紫杉醇脂质体及紫杉醇注射液（10 mg/kg）后的药代动力学进行了研究。结果表明两者血浓经时曲线均符合二室模型，t1/2β分别为5.40 h和2.47 h，其它各参数也发生了明显变化。

A HPLC method was developed for the determination of taxol in ra t blood. The samples were extracted with diethyl ether and separated on a C1 8 co lumn with the mobile phase consisted of methanol-water-acetonitrile.The intern al standard was norethisterone. The detector was set at UV 227 nm. The linear ra nge of the calibration curve is 0.1~120.0 μg/ml and the minimal detectable amou nt is 2.5 ng. The recoveries of taxol are larger than 80.0%,the RSD of interday an d intraday are less than 3.0%. The method has been used in pharmacokinetic studi es of taxol-liposome and free taxol in rat after iv 10 mg/kg. The blood taxol c oncentration-time profile in rat after iv injection of drug in either a solutio n (Cremophor/alcohol,50/50) or a liposome-based formulation follow a bi-expone ntial disposition. T1/2β are 5.40 and 2.47 h respectively, and oth er pharmacokinetic parameters are also different.