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

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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.

Key words： Brucea Milk thistle Human liver microsome Phenytoin Drug interaction

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	CHEN Yue-yue
	LIU Yong
	CHEN Yin-nan
	LI Wei

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CHEN Yue-yue,LIU Yong,CHEN Yin-nan, et al. Inhibitory effect of the main active components of Brucea javanica and Silythistle on the metabolism of Phenytoin[J]. 中国当代医药, 2021, 28(26): 4-7转13.

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http://dangdaiyiyao.com/EN/ OR http://dangdaiyiyao.com/EN/Y2021/V28/I26/4

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