Objective To explore the effects of orientin on the enzyme activity of wild type UDP-glucuronosyltrans-fer-ase1A1(UGT1A1)and its common mutant UGT1A1*6,and to predict the risk of herb-drug interaction between ori-entin and Irinotecan.Methods In vitro incubation system was established,polygonin was incubated with SN-38,the pro-duction rate of SN-38 glucuronide(SN-38G)was determined by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS),and the effect of polygonin on the glucoaldehyde acidification of SN-38 was investigated.Re-sults The half-maximal inhibitory concentration(IC50)of orientin was 19.04 µmol/L for UGT1A1*1 and 34.35 μmol/L for UGT1A1*6,and the calculated Ki values were 9.32 and 19.63 μmol/L,respectively.Quantitative predictions using in vitro-in vivo extrapolation(IVIVE)showed that oral polygonin-containing herbal medicine combined with Irinotecan resulted in an increase of at least 87％in the plasma concentration-time area under curve(AUC)of SN-38.Conclusion Orientin may inhibit the activity of UGT1A1 and lead to the adverse reaction of Irinotecan,which provides a theoretical guide for rational use of Chinese herbal medicine containing orientin and Irinotecan.
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