Abstract: Objective To analyze the effect of simvastatin on the activity of CYP450 in liver by using Cocktail probe drug method, and to provide reference for drug interaction research and promote rational drug use in clinic. Methods The specific probe substrates corresponding to the subtypes of CYP450 enzyme were selected and UPLC-MS was used to determine the drug concentration of the probe drug in plasma. The pharmacokinetic parameters were calculated by DAS 3.0. The effect of simvastatin on CYP450 activity was evaluated by comparing the pharmacokinetic parameters of probe substrates in blank control group and simvastatin group. Results Compared with the blank control group, the AUC of fenacetin in simvastatin group decreased, the AUC of tolbutamide, chlorzoxazone and testosterone increased, and the main pharmacokinetic parameters of omeprazole and metoprolol had no significant difference compared with the blank control group. Conclusion Simvastatin can induce the activity of CYP1A2 in rats, inhibit the activity of CYP2C9, CYP2E1 and CYP3A4, but has no significant effect on the activity of CYP2C19 and CYP2D6.

Key words: Simvastatin, Cocktail probe drug method, CYP450, UPLC-MS, drug interaction