灯盏花素磷脂复合物自微乳在Beagle犬体内药代动力学及生物利用度

目的:建立Beagle犬血浆中灯盏乙素的定量分析方法,测定灯盏乙素在Beagle犬体内血药浓度经时过程,评价灯盏花素磷脂复合物自微乳的药代动力学及相对生物利用度。方法:单剂量分别灌胃给予Beagle犬灯盏花素磷脂复合物自微乳及灯盏花素片,采用HPLC测定血浆中灯盏乙素的浓度,流动相甲醇-0.2%磷酸水(45∶55),检测波长335 nm。运用DAS2.1.1软件程序拟合药物浓度-时间曲线,计算药动学参数和生物利用度。结果:灯盏花素磷脂复合物自微乳、灯盏花素片灌胃Beagle犬后灯盏乙素药-时曲线均符合二室模型,主要药代动力学参数Tmax分别为190 min和160 min,Cmax分别为78.98mg·L-1和33.63 mg·L-1,AUC0-t分别为18 674.619 mg·L-1·min和9 132.475 mg·L-1·min;相对生物利用度204.49%。结论:灯盏花素磷脂复合物自微乳较灯盏花素片能显著提高灯盏乙素在Beagle犬体内的生物利用度,为灯盏花素口服制剂的开发提供新方向。

Pharmacokinetics and Bioavailability of Breviscapine Phospholipid Complex Self-microemulsions in Beagle Dogs

Objective: To establish a quantitative analysis method for pharmacokinetics and bioavailability of breviscapine phospholipid complex self-microemulsions in Beagle dogs. Method: Beagle dogs were administered with breviscapine phospholipid complex self-microemulsions and breviscapine tablets at single dose,respectively.HPLC was adopted to determine the concentration of scutellarin in plasma with mobile phase of methanol-0.2% phosphoric acid solution(45:55) and detection wavelength at 335 nm.Pharmacokinetics parameters and bioavailability was calculated by DAS2.1.1 software program. Result: Plasma concentration-time profiles of scutellarin in these two preparations were fitted to double-compartment model,Tmaxof breviscapine phospholipid complex self-microemulsions and breviscapine tablets were 190 min and 160 min,Cmax were 78.98 mg·L^-1 and 33.63 mg·L^-1,AUC_0-twere 18 674.619 mg·L^-1·min and 9 132.475 mg·L^-1·min,respectively.Relative bioavailability of self-microemulsions relative to tablets was 204.49%. Conclusion: Breviscapine phospholipid complex self-microemulsions can significantly improve bioavailability of scutellarin in Beagle dogs,which provides a new direction for development of oral preparations of breviscapine.