Abstract
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.
Highlights
Baicalin (5, 6-Dihydroxy-flavone-7-O-glucuronide, (Figure 1)) is the major bioactive constituent of Radix scutellariae (Huang-Qin in Chinese), which is widely used in eastern and western medicine [1, 2]
The results indicated that multiple doses of baicalin inhibited the expression of CYP3A2 in rat liver
The results suggested that the lower CL of MDZ when the drugs were administered together could be attributable to the inhibition of hepatic metabolism of MDZ by baicalin inhibition of CYP3A1/2
Summary
Baicalin (5, 6-Dihydroxy-flavone-7-O-glucuronide, (Figure 1)) is the major bioactive constituent of Radix scutellariae (Huang-Qin in Chinese), which is widely used in eastern and western medicine [1, 2]. The inhibition of the drug-metabolising enzyme cytochrome P450 (CYP) is known to participate in this type of interaction. The CYP3A subfamily is by far the most abundant of all the human CYP isoforms [10] and catalyses the metabolism of nearly 60% of clinical drugs [11]. DDIs involving the inhibition of CYP3A are generally considered to be undesirable as they may manifest as unwanted side effects for drugs with a narrow therapeutic window [12, 13]. Recent studies [14, 15] revealed that chemical drugs and natural products such as herbs may inhibit CYP3A activity. The widespread use of baicalin as alternative or complementary medicine has led to increasing concerns with respect to potential herb-drug interactions through its effects on enzymatic pathways
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