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目的:探讨银杏叶提取物对大鼠美托洛尔药动学的影响。方法:将大鼠随机分为美托洛尔组和美托洛尔联合银杏叶提取物组,美托洛尔组口服给予美托洛尔40 mg·kg~(-1),美托洛尔联合银杏叶提取物组口服给予银杏叶片28.8 mg·kg~(-1)(按黄酮醇苷量)和美托洛尔40 mg·kg~(-1)。给药后2,5,10,20,40,60,90,120,240,360,480,720 min股动脉采血,液相色谱串联质谱(LC-MS/MS)测定美托洛尔及代谢物血药浓度。结果:美托洛尔组联合灌胃给予银杏叶提取物与美托洛尔后,美托洛尔Ka和AUC0-t显著降低(P<0.05),tmax显著增加(P<0.05),美托洛尔代谢产物O-去甲基美托洛尔和α-羟基化美托洛尔AUC0-t显著增加(P<0.05),而CL显著减小(P<0.05)。结论:银杏叶提取物能够显著降低美托洛尔的血药浓度,抑制其代谢物O-去甲基美托洛尔和α-羟基化美托洛尔的清除。
Objective: To investigate the effect of Ginkgo biloba extract on metoprolol pharmacokinetics in rats. Methods: The rats were randomly divided into metoprolol group and metoprolol combined with ginkgo biloba extract group. The metoprolol group was given metoprolol 40 mg · kg -1, metoprolol combined Ginkgo biloba extract group was orally administered ginkgo leaf 28.8 mg · kg -1 (according to the amount of flavonoid glycosides) and metoprolol 40 mg · kg -1. Blood samples were collected at 2,5,10,20,40,60,90,120,240,360,480 and 720 min after anesthesia and methotrexate and metabolites were determined by liquid chromatography-tandem mass spectrometry (LC-MS / MS). Results: After metoprolol combined with ginkgo biloba extract and metoprolol, metoprolol Ka and AUC0-t were significantly decreased (P <0.05), tmax was significantly increased (P <0.05), metoprolol Metabolic products O-desmethylmetoprolol and metoprolol a-metoprolol AUC0-t increased significantly (P <0.05), while CL decreased significantly (P <0.05). Conclusion: Ginkgo biloba extract can significantly reduce the plasma concentration of metoprolol and inhibit the clearance of its metabolites O-desmethylmetoprolol and α-hydroxymetaorolol.