To study the in vitro metabolism phenotypes of thiophenorphine,a novel compound.Methods:Approaches of chemical inhibitors and recombinant P450 enzymes were used to determined metabolism phenotypes of thiophenorphine.Results:The results of metabolism phenotypes showed that CYP3A4,CYP1A2,CYP2C 19,CYP2D6 maybe involved in the thiophenorphine metabolism in human liver microsomes,which was confirmed by recombinate expressed CYP450.CYP3A2,CYP1A2,CYP2C11 maybe take part in thiophenorphine metabolism in Wistar rat liver microsomes.Conclusion:The results of metabolism phenotypes in wistar rat and human liver microsomes have a better correlation.Thiophenorphine could be metabolited by several enzyme phenotypes,that would avoid the drug-drug interaction risk in clinical administration.