吉非替尼小鼠体内药代动力学研究

Study on Pharmacokinetics of Gefitinib in Mice

研究吉非替尼在小鼠体内的药动学。方法:小鼠灌胃两种剂量50及32.5 mg/kg后用高效液相色谱法(HPLC)测定不同时间的血药浓度。色谱条件为Thermo ODS-2HYPERSIL色谱柱(4.6mm×250mm,5μm),流动相为V(甲醇)∶V(水(0.1%三乙胺))=75∶25体积比,检测波长为330nm,流速为1.0mL/min。用DAS2.0药动学软件处理数据。结果:吉非替尼血清浓度在1.5~6μg·mL^(-1)内线性良好,最低检出质量浓度为20ng·mL^(-1),高、中、低浓度样品回收率分别为100.06%,99.85%,100.06%。两组剂量的吉非替尼在小鼠体内的药时曲线均符合二室模型,主要药动学参数:半衰期分别为20.49h和20.51h。药时曲线下面积AUC为12.7和8.5mg/(L·h)。表观分布容积V_d为118.2和113.4L·kg^(-1)。平均驻留时间MRT为25.8h。结论:该方法选择性强,方法简单,能够准确测定小鼠给药后的血药浓度,对该药物的临床血药浓度检测和药代动力学研究有一定的参考价值。

This paper reports a study on the pharmacokinetics of gefitinib in mice.After intragastric administration of gefitinib at two doses of 50 and 32.5 mg/kg in mice,the plasma concentration at different times were measured by HPLC.The chromatographic conditions were：Thermo ODS-2 HYPERSIL column（4.6mm × 250 mm,5μm）with a mobile phase of methanol-water（0.1% triethylamine）=（75∶25）,detection wavelength was at 330 nm,the flow rate was 1.0 mL/min.Data were processed with DAS2.0 pharmacokinetic software.Results show that the concentration of gefitinib was linear in the range of 1.5 ~ 6μg·mL^（-1）.The lowest detectable concentration was 20ng·mL^（-1）.The recoveries of gefitinib were 100.06%,99.85% and 100.06% respectively.The pharmacokinetic parameters of gefitinibin two groups of mice,T_（1/2） is 20.49 and 20.51 h.The area under the curve AUC（mg·L^（-1）· h（-1）） was 12.7 and 8.5.The apparent distribution volume Vd（L·kg^（-1））was 118.2 and 113.4.The average residence time MRT（h）was 25.8.It is concluded that the method has the advantages of high selectivity,simple,accurate and has certain reference value for the clinical blood drug concentration detection and pharmacokinetic study.