ABSTRACT
Objective To investigate the effects of omeprazole on the expression and the activity of CYP2C19 in HepG2 cells. Methods MTT assay was performed to screen the concentration range of omeprazole which did not inhibit HepG2 cell proliferation. Real-time quantitative polymerase chain reaction(Q-PCR)were carried out to determine the effects of omeprazole(0,0.1,1 and 10 mg/L)on the expression of CYP2C19 mRNA,Western blot was carried out to determine the effect of(0,0.1,1 and 10 mg/L)on the ex?pression of CYP2C19 protein. After incubation of different concentrations of omeprazole(0,0.1,1,10 and 100 mg/L)with microsomes prepared from insect cells expressing human P450 isozyme,the fluorescence of the samples was detected in a plate reader to analyze if omeprazole inhibited the CYP2C19 activity. Results Omeprazole could down-regulate CYP2C19 mRNA and protein expressions of HepG2 cells in a dose-dependent manner. When the concentration of omeprazole reached 10 or 100 mg/L,the fluorescence intensities obviously decreased,indicating inhibited CYP2C19 activity. Conclusion Omeprazole inhibits the expression and the activity of CYP2C19 in HepG2 cell. When omeprazole is used in combination with drugs activated via CYP2C19 metabolism,their interaction should be considered carefully.