Background: CYP/CYP450 2C19 (CYP2C19) is a highly polymorphic enzyme and exhibits individual differences in metabolic activity. The purpose of this research was mainly to explore the catalytic activities of 30 CYP2C19 variants on the substrate voriconazole in vitro, including 24 novel CYP2C19 variants (2C19.2E-.2H, .2J, .3C, .29-.33, L16F, 35FS, R124Q, R125G, T130M, N231T, M255T, R261W, N277K, S303N, I327T, N403I, and A430V) found in Chinese Han population for the first time. 
Methods: These CYP2C19 variants were expressed in Spodoptera frugiperda  (Sf ) 21 insect cells using the baculovirus-mediated expression system. The substrate voriconazole was incubated with the abovementioned proteins at 37°C for 30 minutes in an appropriate designed system. Then through detecting its major metabolite voriconazole N-oxide by ultra-performance liquid chromatography tandem mass spectrometry, available data were obtained to explain the influence of CYP2C19  polymorphisms on voriconazole. 
Results: From the results, when compared to CYP2C19.1, most variants exhibited either reduced V_max  and/or increased K_m  value, indicating that the intrinsic clearance (V_max /K_m ) values of most variants were significantly altered. The catalytic activities of 20 novel variants exhibited decreases in different degrees compared to CYP2C19.1, with relative clearance values ranging from 1.11% to 83.78%. However, L16F exhibited the increased catalytic activity for 135.68%. In addition, the kinetic parameters of four variants (2C19.2H, .3, 35FS, and R124Q) could not be detected, due to the defective gene. 
Conclusion: This is the first study to report the effects of CYP2C19  polymorphisms on voriconazole metabolism in vitro, and we hope these data could lay the foundation for the early clinical research and individualized treatment.
Keywords: polymorphisms, CYP2C19, voriconazole, voriconazole N-oxide, drug metabolism