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Background：Cytochrome P450 (P450) is the largest family of enzymatic proteins in the human liver, and its features have been studied in physiology, medicine, biotechnol-ogy, and phytoremediation. OBJECTIVE The aim of this study was to assess the catalytic activities of 28 human CYP3A4 alleles by using dronedarone as a probe drug in vitro, including 7 novel al-leles recently found in the Han Chinese population. METHODS We expressed 28 CYP3A4 alleles in insect microsomes and incubated them with 1-100 μM of dronedarone at 37℃ for 40 minutes to obtain the metabolites of N-debutyl-dronedarone. RESULTS Compared with the wild type of CYP3A4, the 27 defective alleles can be clas-sified into four categories. Three alleles had no detectable enzyme activity leading to a lack of kinetic parameters of N-debutyl-dronedarone; Other three alleles were slightly despaired when it comes to intrinsic clearance values compared with the features of the wild type. Sixteen alleles exhibited 35.91%~79.70% relative values (in comparison to the wild-type) and could be defined as the "moderate decrease group". The rest of the alleles showed a considerable decrease in intrinsic clearance values, ranging from 11.88%~23.34%. Therefore they were classified as a "significantly decreased group". More specifically, 18 CYP3A4 alleles exhibited a substrate inhibition trend toward dronedarone when the concentration rises to 20μM. CONCLUSION The outcomes of this novel study on the metabolism of dronedarone by CYP3A4 alleles can be used as experimental data support for the individualized use of this modern drug.