Department of Pharmacy, the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 600 Yi Shan Road, Shanghai 200233, PR China.
J Ethnopharmacol. 2012 Jan 6;139(1):104-9. doi: 10.1016/j.jep.2011.10.019. Epub 2011 Nov 2.
Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis.
The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs.
Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis.
There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down.
The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.
草药注射剂对大鼠细胞色素 P450 酶的体内作用：一种潜在的药物相互作用风险评估
本研究旨在通过评估其与合用药物相互作用的潜力，研究注射用灯盏花素（HEI）对大鼠细胞色素 P450 酶（CYP1A2、CYP2C11、CYP2D4、CYP2E1 和 CYP3A2）的体内作用，以评估其安全性。
将大鼠随机分为五组，通过尾静脉分别以 1.8ml/kg 或 7.2ml/kg 的剂量每日一次连续给药 3 天或 14 天。第四天或第十五天，所有大鼠通过舌静脉注射 5ml/kg 的鸡尾酒溶液，该溶液包含咖啡因（2.5mg/kg）、甲苯磺丁脲（2.5mg/kg）、氯唑沙宗（5mg/kg）、咪达唑仑（5mg/kg）和酒石酸美托洛尔（10mg/kg）。然后在一组时间点采集 0.8ml 血样。通过 HPLC 同时测定探针药物的血浆浓度。使用 DAS 软件模拟药代动力学参数，评估 HEI 对大鼠 CYP1A2、CYP2C11、CYP2D4、CYP2E1 和 CYP3A2 酶活性的影响。采用 ANOVA 和 Dunnett 检验进行数据分析。
HEI 预处理大鼠的咖啡因、甲苯磺丁脲和氯唑沙宗的药代动力学参数无显著影响。但 HEI 预处理大鼠的酒石酸美托洛尔和咪达唑仑的许多药代动力学参数均受到显著影响（P<0.05），表明这些治疗组中美托洛尔和咪达唑仑的代谢明显减慢。
本体内研究结果表明，HEI 对大鼠 CYP1A2、CYP2C11 和 CYP2E1 无影响，但对大鼠 CYP2D4 和 CYP3A2 有潜在的抑制作用。因此，临床中当 HEI 与经人 CYP2D6 或 CYP3A4 代谢的药物合用时需谨慎，可能会导致这些药物的浓度增加，出现相关的草药-药物相互作用。
