In vitro inhibitory effects of sophocarpine on human liver cytochrome P450 enzymes.

1. Sophocarpine is a biologically active component isolated from the foxtail-like sophora herb and seed that is often orally administered for the treatment of cancer and chronic bronchial asthma. However, whether sophocarpine affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. 2. In this study, the inhibitory effects of sophocarpine on the eight human liver CYP isoforms (CYP1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs). 3. The results indicate that sophocarpine could inhibit the activity of CYP3A4 and 2C9, with the IC50 values of 12.22 and 15.96 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that sophocarpine is not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2C9, with Ki values of 6.74 and 9.19 μM, respectively. Also, sophocarpine is a time-dependent inhibitor of CYP3A4 with Kinact/KI value of 0.082/21.54 μM-1 min-1. 4. The in vitro studies of sophocarpine with CYP isoforms suggested that sophocarpine has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.