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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 AUC 0− ∞   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 AUC 0− ∞   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.

Inhibitory Effects of Baicalin on the Expression and Activity of CYP3A Induce the Pharmacokinetic Changes of Midazolam in Rats