Abstract: In vitro liver microsomal incubation system was used to investigate the metabolic stability of piperine in liver microsomes of human,SD rats,mice,Rhesus monkeys and Beagle dogs,compare the metabolic difference between differenct species and determine the metabolic phenotype of piperine in human liver microsomes.Selective chemical inhibition was used to investigate the metabolic phenotype of piperine in human liver microsomes.The remaining concentrations of piperine incubated in various species of liver microsomes were determined by UFLC-MS / MS,and evaluated their metabolic stability and in vitro pharmacokinetic parameters.Selective chemical inhibition was used to predict the metabolic phenotype of piperine in human liver microsomes.It can be speculated that the half-life of piperine in the liver microsomes of SD rats,mice,rhesus monkeys,and Beagle dogs respectively were 31.36,48.46,138.60,147.45,and 165.00 min;The ininsic clearance rate was 0.044 2,0.028 6,0.010 0,0.009 4 and 0.008 4 mL/(mL·mg);In human liver microsomes,piperine was mainly metabolized by CYP3A4 and CYP2C9 enzymes.The results showed that the metabolism of piperine in all kinds of liver microsomes is relatively stable,the metabolic properties of liver microsomes in rat is similar mostly to human.It can be considered that metabolism results from rats can be used to predict human metabolic results in subsequent experiments.The results showed that CYP3A4 and CYP2C9 primary participate in metabolism of piperine.

Key words: piperine, metabolic stability, metabolic phenotype, metabolite, liver microsomes