Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Daxue Road 40, Zhengzhou, Henan 450052, China.
Evid Based Complement Alternat Med. 2013;2013:179643. doi: 10.1155/2013/179643. Epub 2013 Apr 24.
Baicalin, a flavonoid compound isolated from Scutellaria baicalensis, has been shown to possess antiinflammatory, antiviral, antitumour, and immune regulatory properties. The present study evaluated the potential herb-drug interaction between baicalin and midazolam in rats. Coadministration of a single dose of baicalin (0.225, 0.45, and 0.90 g/kg, i.v.) with midazolam (10 mg/kg, i.v.) in rats resulted in a dose-dependent decrease in clearance (CL) from 25% (P < 0.05) to 34% (P < 0.001) with an increase in AUC0-∞ from 47% (P < 0.05) to 53% (P < 0.01). Pretreatment of baicalin (0.90 g/kg, i.v., once daily for 7 days) also reduced midazolam CL by 43% (P < 0.001), with an increase in AUC0-∞ by 87% (P < 0.01). Multiple doses of baicalin decreased the expression of hepatic CYP3A2 by approximately 58% (P < 0.01) and reduced midazolam 1'-hydroxylation by 23% (P < 0.001) and 4'-hydroxylation by 21% (P < 0.01) in the liver. In addition, baicalin competitively inhibited midazolam metabolism in rat liver microsomes in a concentration-dependent manner. Our data demonstrated that baicalin induced changes in the pharmacokinetics of midazolam in rats, which might be due to its inhibition of the hydroxylation activity and expression of CYP3A in the liver.
黄芩苷是从黄芩中分离得到的一种黄酮类化合物，具有抗炎、抗病毒、抗肿瘤和免疫调节作用。本研究评估了黄芩苷与咪达唑仑在大鼠体内的潜在草药-药物相互作用。在大鼠中，单次给予黄芩苷（0.225、0.45 和 0.90 g/kg，静脉注射）与咪达唑仑（10 mg/kg，静脉注射）合用，导致清除率（CL）呈剂量依赖性降低，从 25%降低至 34%（P < 0.05），AUC0-∞从 47%增加至 53%（P < 0.01）。黄芩苷（0.90 g/kg，静脉注射，每日一次，共 7 天）预处理也使咪达唑仑 CL 降低 43%（P < 0.001），AUC0-∞增加 87%（P < 0.01）。黄芩苷多次给药使肝 CYP3A2 的表达减少约 58%（P < 0.01），并使咪达唑仑在肝内 1'-羟化作用减少 23%（P < 0.001）和 4'-羟化作用减少 21%（P < 0.01）。此外，黄芩苷以浓度依赖性方式竞争性抑制大鼠肝微粒体中咪达唑仑的代谢。我们的数据表明，黄芩苷改变了咪达唑仑在大鼠体内的药代动力学，这可能是由于其抑制了肝脏中 CYP3A 的羟化活性和表达。
