An inhibition study of beauvericin on human and rat cytochrome P450 enzymes and its pharmacokinetics in rats

作者：Mei, Li; Zhang, Lixin; Dai, Renke^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2009, 24(3): 753-762.

DOI：10.1080/14756360802362041

• Inhibition
• cytochrome P450
• beauvericin
• pharmacokinetic
• antifungal effect

Beauvericin is a secondary metabolite natural product from microorganisms and has been shown to have a new potential antifungal activity. In this study, the metabolism and inhibition of beauvericin in human liver microsomes (HLM) and rat liver microsomes (RLM) were investigated. The apparent K-m and V-max of beauvericin in HLM were determined by substrate depletion approach and its inhibitory effects on cytochromes P450 (CYP) activities were evaluated using probe substrates, with IC50 and the (K-i) values were 1.2 mu M (0.5 mu M) and 1.3 mu M (1.9 mu M), respectively for CYP3A4/5 (midazolam) and CYP2C19 (mephenytoin). Similarly, beauvericin was also a potent inhibitor for CYP3A1/2 (IC50: 1.3 mu M) in RLM. Furthermore, the pharmacokinetics of beauvericin in the rat were studied after p.o administration alone and co-administration with ketoconazole, which indicated a pharmacodynamic function may play a role in the synergistic effect on antifungal activity.

• 出版日期2009
• 单位中国科学院微生物研究所