Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, China.
Chin J Nat Med. 2013 May;11(3):302-8. doi: 10.1016/S1875-5364(13)60033-3.
To assess the effects of Radix Bupleuri and vinegar-baked Radix Bupleuri on cytochrome 450 activity of rats.
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.
The AUC and T1/2 of midazolam, dextromethorphan and chlorzoxazone decreased significantly (P < 0.05) in rats after different dosing of Radix Bupleuri or vinegar-baked Radix Bupleuri for seven days. Treatment of Radix Bupleuri decreased T1/2 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.
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.
评估柴胡及醋柴胡对大鼠细胞色素 450 活性的影响。
连续 7 天给大鼠不同剂量的柴胡或醋柴胡后，同时给予 6 种探针药物（咖啡因、咪达唑仑、右美沙芬、甲苯磺丁脲、奥美拉唑、氯唑沙宗）。采用高效液相色谱-三重四极杆质谱联用（HPLC-MS/MS）法测定 6 种探针的血药浓度，并计算其相应的药代动力学参数。
连续 7 天给大鼠不同剂量的柴胡或醋柴胡后，咪达唑仑、右美沙芬和氯唑沙宗的 AUC 和 T1/2 显著降低（P < 0.05）。柴胡处理降低了奥美拉唑的 T1/2 和 AUC，但醋柴胡的正常剂量处理并未改变奥美拉唑的药代动力学。所有醋柴胡处理的甲苯磺丁脲的药代动力学与对照大鼠相比无统计学差异（P > 0.05），然而，柴胡处理降低了甲苯磺丁脲的 T1/2。所有柴胡或醋柴胡处理的大鼠的咖啡因药代动力学与对照大鼠相比无统计学差异（P > 0.05）。
柴胡和醋柴胡对 CYP2C9 和 CYP2C19 有不同的影响。柴胡和醋柴胡对 CYP2E1、CYP2D6 和 CYP3A4 有很强的诱导作用，但对 CYP1A2 没有影响。柴胡和醋柴胡提取物疗效不同的原因可能是柴胡和醋柴胡对 CYP2C9 和 CYP2C19 的不同作用。
