Effect Of Coumarins On CYP450s In Human Liver Microsomes

Objective: To find the effect of four coumarins on the activities of CYP2A6, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP1A2 and CYP2E1 in human liver microsomes.Methods: Probe drugs of CYP2A6, CYP3A4, CYP2C9, CYP2C19, CYP2D6, CYP1A2 and CYP2E1 were incubated with or without coumarins with NADPH- generating system respectively to study the effect on CYP450s activities in human liver microsomes. In this study we set four concentrations (6.25, 12.5, 25, 50 uM) for psoralen and isopsoralen ,and (5, 10, 20, 40 uM) for imperatorin and isoimperatorin. All the incubations throughout the study were carried out in triplicate.Results: All four coumarins show inhibition to CYP2A6 when they are in the higher concentration. And imperatorin and isoimperatorin exhibit inhibition to CYP1A2 and CYP2E1 in every concentration. This result not only shows that the coumarin chemicals certainly have some effects to human CYP450s,but also remind us that possible drug interactions should take into account when combined with the drugs metablized by these enzymes.