Caco-2细胞模型不同取样方式对药物表观渗透系数的影响

Effects of different sampling methods on P values of drugs

目的验证Caco-2细胞模型中不同取样方式对药物表观渗透系数(Papp)的影响。方法采用已知高渗模型药物酒石酸美托洛尔、中渗模型药物阿替洛尔,未知渗透性药物甲硝唑,在Caco-2细胞模型中,从BL侧分别进行间隔取样与单次取样,取样后离心,取上清液并采用HPLC法测定3种药物的含量,计算并比较3种药物两种取样方式的Papp值。结果酒石酸美托洛尔、阿替洛尔、甲硝唑间隔取样和单次取样的Papp值分别为:1.796×10^-5±1.960×10^-6、4.076×10^-7±3.580×10^-8、2.047×10^-5±2.420×10^-6、1.937×10^-5±1.720×10^-6、4.614×10^-7±4.810×10^-8、2.072×10^-5±1.650×10^-6cm·s-1。结论实验中,间隔取样与单次取样对于药物Papp值的差异无统计学意义。

OBJECTIVE To verify the effect of different sampling methods on the apparent permeability coefficient(Papp)of the drug in the Caco-2 cell monolayer model.METHODS Metoprolol tartrate with high permeability,atenolol with middle permeability and metronidazole were used.In the Caco-2 cell monolayer model,interval sampling and single sampling were performed from the BL side.Samples were centrifuged and the content of the three drugs in the supernatant was determined by HPLC.Pappvalues were calculated.RESULTS The Pappvalues of meroprolol tartrate,atenolol and metronidazole were 1.796×10^-5±1.960×10^-6,4.076×10^-7±3.580×10^-8,and 2.047×10^-5±2.420×10^-6cm·s-1by interval sampling,1.937×10^-5±1.720×10^-6,4.614×10^-7±4.810×10^-8,and 2.072×10^-5±1.650×10^-6cm·s-1by single sampling,separately.CONCLUSION In this experiment,there is no statistically significant difference between the interval sampling and the single sampling for the drugs Pappvalue.