Huang Y, Zheng S-L, Xu Z-S, Hou Y
Department of General Surgery of Wenzhou People's Hospital, Wenzhou, China.
Department of Pediatric Surgery of the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Drug Res (Stuttg). 2014 Aug;64(8):424-8. doi: 10.1055/s-0033-1361107. Epub 2013 Nov 27.
Gastrodia elata Blume (GE) has been used as a traditional herb and is considered one of the most important medicinal plants in Oriental countries since centuries.
The purpose of this study was to find out the differences between the effects of unprocessed and cooked-processed GE (CGE) on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9 and CYP3A4) by using cocktail probe drugs in vivo.
A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (10 mg/kg), was orally administration to rats treated with GE or CGE for 14 days orally. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0.
Both GE and CGE did not have significant influences on the pharmacokinetic parameters of phenacetin (P>0.05). In addition, CGE decreased the t1/2, Cmax, AUC(0-∞) of tolbutamide (P<0.05) and it increased CL significantly (P<0.01). Furthermore, the trend in CGE was similar but far more significant than GE on t1/2, Cmax, AUC(0-∞), and other parameters of midazolam (P<0.05).
In conclusion, GE and CGE had no effects on rat CYP1A2. GE did not affect CYP2C9 activity, but CGE induced the CYP2C9 activity. Moreover, CGE was more potent than GE for inhibitory effect on CYP3A4 activity. These results provide useful scientific data for the safe clinical application of either extract of GE or in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.
天麻自古以来就在东方国家被用作传统草药，被认为是最重要的药用植物之一。
本研究旨在通过体内使用鸡尾酒探针药物，找出未加工和炮制后的天麻（CGE）对大鼠细胞色素P450（CYP）酶（CYP1A2、CYP2C9和CYP3A4）影响的差异。
将含有非那西丁（20mg/kg）、甲苯磺丁脲（5mg/kg）和咪达唑仑（10mg/kg）的5mL/kg剂量鸡尾酒溶液口服给予经天麻或炮制天麻处理14天的大鼠。在一系列时间点采集血样，通过HPLC-MS/MS测定血浆中探针药物的浓度。用DAS 2.0软件计算相应的药代动力学参数。
天麻和炮制天麻对非那西丁的药代动力学参数均无显著影响（P>0.05）。此外，炮制天麻降低了甲苯磺丁脲的t1/2、Cmax、AUC(0-∞)（P<0.05），并显著增加了CL（P<0.01）。此外，炮制天麻对咪达唑仑的t1/2、Cmax、AUC(0-∞)和其他参数的影响趋势与天麻相似，但更为显著（P<0.05）。
总之，天麻和炮制天麻对大鼠CYP1A2均无影响。天麻不影响CYP2C9活性，但炮制天麻诱导CYP2C9活性。此外，炮制天麻对CYP3A4活性的抑制作用比天麻更强。这些结果为天麻提取物单独或与其他药物联合安全临床应用提供了有用的科学数据，应可避免其他草药-药物相互作用引起的副作用。
