胡黄连苷Ⅱ对大鼠体内P450酶活性的影响

目的：研究胡黄连苷Ⅱ对大鼠体内P450酶活性的影响。方法：采用多探针技术，测定单次和多次使用胡黄连苷Ⅱ前后大鼠血浆中相应的探针药物咪哒唑仑、奥美拉唑、双氯芬酸、氯唑沙腙和右美沙芬的浓度及其药代动力学参数。结果：大鼠单次给予胡黄连苷Ⅱ（10mg．kg^-1）后，探针药物的浓度及其药代动力学参数均没有显著性变化。按每天两次，每次10mg．kg^-1剂量灌胃胡黄连苷Ⅱ，连续12d后，与用药前比较，咪哒唑仑、双氯芬酸、右美沙芬和氯唑沙宗的血药浓度及其药代动力学参数未见显著性改变；但奥美拉唑的血药浓度及其AUC0-t有升高的趋势（p〈0．05）。结论：单次给予胡黄连苷Ⅱ对大鼠P450活性没有影响，而多次给予胡黄连苷Ⅱ对大鼠CYP2C19的活性有抑制作用。

Investigation of Picroside II's Impacts on the P450 Activities Using a Cocktail Method.

AIM:To evaluate the effects of picroside II on P450 activities in rats.METHODS:Five probe drugs(diclofenac,midazolam,dextromethorphan,chlorzoxazone and omeprazole)were simultaneously given to rats after single and multiple dosing of picroside II.The plasma concentrations of the five probes were measured by LC-MS and their corresponding pharmacokinetic parameters were calculated.RESULTS:There were no differences among the five probes in their plasma concentrations and the corresponding pharmacokinetic parameters in rats after single dosing of picroside II(10 mg·kg-1).The AUC0-1 and the drug concentration of omeprazole increased significantly(P＜0.05) in rats after multiple dosing of picroside II(10 mg-kg-1,orally,twice daily for 12 consecutive days).CONCLUSION:Single administration of picroside II had very Little impact on the activities of P450 while multiple administration of picroside II tended to inhibit CYP2C19 activity.