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成颖, 黄寅, 田媛, 许磊, 刘国强, 张尊建. 探针药物法评价柴胡生品及醋炙品对细胞色素P450酶的影响[J]. 中国天然药物, 2013, 11(3): 302-308.
引用本文: 成颖, 黄寅, 田媛, 许磊, 刘国强, 张尊建. 探针药物法评价柴胡生品及醋炙品对细胞色素P450酶的影响[J]. 中国天然药物, 2013, 11(3): 302-308.
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CHENG Ying, HUANG Yin, TIAN Yuan, XU Lei, LIU Guo-Qiang, ZAHNG Zun-Jian. Assessment of the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity by a six-drug cocktail approach[J]. Chinese Journal of Natural Medicines, 2013, 11(3): 302-308.
Citation: CHENG Ying, HUANG Yin, TIAN Yuan, XU Lei, LIU Guo-Qiang, ZAHNG Zun-Jian. Assessment of the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity by a six-drug cocktail approach[J]. Chinese Journal of Natural Medicines, 2013, 11(3): 302-308.
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探针药物法评价柴胡生品及醋炙品对细胞色素P450酶的影响

Assessment of the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity by a six-drug cocktail approach

    摘要
  • 摘要: 目的:研究柴胡生品及醋炙品对细胞色素P450酶的影响。方法:采用多探针技术,应用高效液相色谱-三重四级杆串联质谱(HPLC-MS/MS)测定连续给予7天柴胡生品或醋炙品前后大鼠血浆中相应的探针药物咪达唑仑、奥美拉唑、甲苯磺丁脲、氯唑沙宗、右美沙芬和咖啡因的浓度及其药代动力学参数。结果:连续7天给予柴胡生品或醋炙品后,咪达唑仑、氯唑沙宗和右美沙芬的血药浓度均显著下降,AUC和T1/2显著减小(P结论:柴胡生品及醋炙品对CYP2E1、CYP2D6和CYP3A4均产生诱导作用,对CYP1A2不产生诱导作用;柴胡生品及醋炙品对CYP2C9和CYP2C19的影响存在差异,这种差异可能是柴胡经炮制后作用发生变化的原因。

     

    Abstract: AIM:To assess the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity of rats.METHODS:Six probe drugs(caffeine,midazolam,dextromethorphan,tolbutamide,omeprazole,chlorzoxazone) were simultaneously given to rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days.The plasma concentrations of the six probes were measured by high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-MS/MS) and their corresponding pharmacokinetic parameters were calculated.RESULTS:The AUC and T1/2 of midazolam,dextromethorphan and chlorzoxazone decreased significantly(PT1/2 and AUC of omeprazole,but treatment of vinegar-baked Radix Bupleuri with normal dose did not change the pharmacokinetics of omeprazole.The pharmacokinetics of tolbutamide in all vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference(P>0.05) from that of controlled rats,however,treatment of Radix Bupleuri decreased tolbutamide T1/2.The pharmacokinetics of caffeine in all Radix Bupleuri or vinegar-baked Radix Bupleuri-treated rats showed no statistically significant difference(P>0.05) from that of controlled rats.CONCLUSION:The Radix Bupleuri and vinegar-baked Radix Bupleuri have different effects on the CYP2C9 and CYP2C19.Radix Bupleuri and vinegar-baked Radix Bupleuri have strong induction effects on the CYP2E1,CYP2D6 and CYP3A4,however,have no impact on CYP1A2.The reason of different therapeutic effects of Radix Bupleuri and vinegar-baked Radix Bupleuri extract may be the different effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on the CYP2C9 and CYP2C19.

     

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