title: Concentration-dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats.
abstract: Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti-cancer and anti-inflammatory properties. In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and CYP3A, in rats. Lineweaver-Burk plots demonstrated that baicalin inhibited the activities of CYP2D and CYP3A in a non-competitive manner in rat liver microsomes (RLMs). Concomitant administration of baicalin (0.90 g/kg, i.v.) and DXM (10 mg/kg, i.v.) increased the maximum drug concentration (C(max)) (37%) and the area under concentration-time curve (AUC) (42%) and decreased the clearance (CL) (27%) of DXM in a randomised, crossover study in rats (P < 0.01). The change in the AUC of DXM was significantly correlated with the C(max) and AUC of baicalin (P < 0.05). The inhibitory effects of multiple doses of baicalin (0.90 g/kg, i.v., 12 days) on the metabolism of DXM were similar to those observed following a single dose in rats. The activity of CYP3A in excised liver samples from rats following multiple baicalin treatment was significantly decreased compared to that of the control group (P < 0.05), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D. Taken together, these data demonstrate that baicalin inhibits the metabolism of DXM in a concentration-dependent manner in rats, possibly through inhibiting hepatic CYP2D and CYP3A activities.
authors: Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, People's Republic of China.
authors: Xin
authors: X
authors: Tian
authors: Zhen-Yu
authors: ZY
authors: Cheng
authors: Jing
authors: J
authors: He
authors: Lin-Jing
authors: LJ
authors: Jia
authors: Hai-Ling
authors: HL
authors: Qiao
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D003915:Dextromethorphan / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis / Q000737:chemistry
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; C038044:baicalin; D003915:Dextromethorphan; D051544:Cytochrome P-450 CYP3A