Effect of Inula cappa on CYP450 Enzyme in Rats by Cocktail Probe Drugs / 中国实验方剂学杂志

ABSTRACT

Objective:To study on the effect of Inula cappa extract on the activities of six cytochrome P450(CYP450) enzymes in rats by Cocktail probe method. Method:Rats in the I. cappa high and low dose groups were given oral administration of active fractions of I. cappa at a dose of 8.127,2.709 g·kg-1·d-1 of the material for 7,14 d,repectively.Probe drugs(caffeine,midazolam,tolbutamide,omeprazole,metoprolol,chlorzoxazone) were simultaneously injected to rats after administration.Plasma was collected at different time after the administration of probe drugs.The plasma concentrations of these six probes were measured by UPLC-MS and their corresponding pharmacokinetic parameters were calculated with DAS 2.0. Result:Compared with the control group,only the apparent volume of distribution(V) of midazolam was increased;area under the curve(AUC0-t and AUC0-∞)and half-life period(T1/2) of caffeine,midazolam,tolbutamide and omeprazole were increased and the clearance rate(CL) of them was decreased in rats of I. cappa groups.But there were no differences in pharmacokinetic parameters of chlorzoxazone and metoprolol. Conclusion:I. cappa can reduce the enzymatic activities of CYP3A,CYP1A2,CYP2C9 and CYP2C19 in rats at different degree,among which CYP3A is the strongest.