Inhibitory effect of the main active components of Brucea javanica and Silythistle on the metabolism of Phenytoin
CHEN Yue-yue1 LIU Yong2 CHEN Yin-nan1 LI Wei1▲
1.Translational Medicine Research Institute,College of Medicine,Yangzhou University,Jiangsu Province,Yangzhou 225009,China;
2.School of Life and Pharmaceutical Sciences,Dalian University of Technology,Liaoning Province,Panjin 124221,China
Abstract：Objective To evaluate whether the main components of Brucea and Milk thistle will inhibit Phenytoin metabolism in human liver microsomes.Methods Ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to determine the formation rate of 5-(4-hydroxyphenyl)-5-phenylacetonitroide(P-HPPH),a metabolite of phenytoin,in ESI positive mode.The alteration of p-HPPH formation rate was employed to evaluate the inhibitory effect of brusatol,bruceine D,silybin A and silybin B on Phenytoin metabolism by human liver microsomes.Results Silybin A potently inhibited human liver microsomes catalyzed phenytoin metabolism with an IC50 values of 7.67 μmol/L.Silybin B was a moderate inhibitor with an IC50 values of 15.49 μmol/L.Brusatol and bruceine D showed no significant inhibitory effect.Conclusion In order to avoid drug interaction caused by adverse clinical response,the combination of silybin A and silybin B with antiepileptic drug phenytoin should be avoided.
陈悦悦；刘勇；陈银楠；李巍. 鸦胆子和水飞蓟主要活性成分对苯妥英代谢的抑制作用研究[J]. 中国当代医药, 2021, 28(26): 4-7转13.
CHEN Yue-yue； LIU Yong； CHEN Yin-nan； LI Wei. Inhibitory effect of the main active components of Brucea javanica and Silythistle on the metabolism of Phenytoin. 中国当代医药, 2021, 28(26): 4-7转13.
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