论文题目: | Drug-drug Interactions between Ketoconazole and Berberine in Rats: Pharmacokinetic Effects Benefit Pharmacodynamic Synergism |
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作者: | Zhou, YM; He, P; Liu, AM; Zhang, LX; Liu, YD; Dai, RK |
联系作者: | Dai, RK |
刊物名称: | PHYTOTHERAPY RESEARCH |
期: | 5 |
卷: | 26 |
页: | 772-777 |
年份: | 2012 |
影响因子: | 2.086 |
论文下载: | |
摘要: | Ketoconazole (KTZ), a clinical antifungal agent, is a known inhibitor of CYP3A and permeability glycoprotein (P-gp). Berberine (BBR), a natural plant-derived product used for gastroenteritis, is a substrate of P-gp. Recently, a synergistic antifungal effect of KTZ combined with BBR has been revealed. In this study, we performed both in vivo and in vitro experiments to explore whether pharmacokinetic interactions between KTZ and BBR would benefit their phamacodynamic synergism. After oral co-administration of 10?mg/kg KTZ with 60?mg/kg BBR, the average area under the curve (AUC) and the maximum concentration (Cmax) for KTZ increased to 215% and 449% (p?0.05), respectively, in male rats and 157% and 172% (p?0.05), respectively, in female rats, compared with those administered KTZ alone. Area under the curve and Cmax for BBR increased to 173% and 142%, respectively, compared with those administered BBR alone. After intravenous co-administration of 0.5?mg/kg KTZ and 0.8?mg/kg BBR, the pharmacokinetic properties of KTZ remained the same, but AUC of BBR increased to 254% (p?0.05) compared with those administered BBR alone. In rat liver microsomes, inhibitory concentration (IC)50 of BBR inhibiting KTZ depletion was determined to be 103?mu m. These resulting pharmacokinetic interactions may benefit their pharmacodynamic synergism to a certain extent. Copyright (c) 2011 John Wiley & Sons, Ltd. |
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