Abstract
The effect of agrimoniin on the activity of cytochrome P450 (CYP450) enzymes would induce drug-drug interaction, which leads to adverse effects or even failure of therapy. Agrimoniin was incubated with the specific substrates of eight human liver CYP isoforms in pooled human liver microsomes. The enzyme kinetics and time-dependent study were performed to obtain kinetic parameters and characteristics in vitro. Agrimoniin significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC50 values of 6.26, 9.35, and 8.30 μM, respectively. Agrimoniin served as a non-competitive inhibitor of CYP3A4 and a competitive inhibitor of CYP1A2 and 2D6. Moreover, the incubation time also significantly affected the inhibition of CYP3A4. In vitro inhibitory effect of agrimoniin on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. The potential drug-drug interactions between agrimoniin and drugs metabolised by CYP1A2, 2D6, and 3A4 should be paid special attention.
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