Inhibition Effect of Spinosin on Cytochrome P450 Enzymes from Human Liver Microsomes in vitro / 中国药房

ABSTRACT

OBJECTIVE:To study the inhibition effect of spinosin on 7 subtypes (CYP2B6,CYP2C8,CYP2C9,CYP2D6, CYP1A1,CYP2C19 and CYP3A4)of cytochrome P450(CYP450)enzymes from human liver microsomes in vitro. METHODS:Tak-ing 200.00,100.00,50.00,25.00,12.50,6.25,3.13,1.56,0.78,0.39 μmol/L spinosin and human liver microsomes for incuba-tion,using daktarin,bupropion,amodiaquine hydrochloride,diclofenac sodium,mephenytoin,dextromethorphan hydrobromide and midazolam as the specific probe drugs for above-mentioned 7 subtypes of CYP450 enzymes. UPLC-Q-TOF-MS was conducted to detect generation amount of 7 probe drug metabolites,and the half inhibitory concentration (IC50) of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes was calculated. RESULTS:IC50 of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes were 1714,1158,226.1,2288,80.59,101.1,1119 μmol/L,respectively,which were higher than 50μmol/L. CONCLUSIONS:Spinosin has no inhibition effect on above-mentioned 7 subtypes of CYP450 enzymes from human liver microsomes,with very low probability of inducing metabolic drug interactions.