effect of pachymic acid on the activity of Cytochrome P450 enzymes.

Pachymic acid is a wildly used traditional Chinese medicine with various pharmacological features. It also exists in many drugs which are wildly used in pediatric.The effect of pachymic acid on the activity of eight major CYP isoforms was investigated in human liver microsomes.The effects of pachymic acid on eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated using human liver microsomes (HLMs), and the enzyme kinetic parameters were calculated.The activity of CP3A4, 2E1, and 2C9 was inhibited by pachymic acid in a concentration-dependent manner with values of 15.04, 27.95, and 24.22 μM, respectively. Pachymic acid is a non-competitive inhibitor of CYP3A4, with the value of 6.47 μM. While the inhibition of CYP2E1 and 2C9 was performed in a competitive manner, with the value of 11.96 and 10.94 μM, respectively. Moreover, the inhibition of CYP3A4 was in a time-dependent manner with the / value of 7.77/0.048 minμM.The inhibitory effect of pachymic acid on the activity of CYP3A4, 2E1, and 2C9 indicated the potential drug-drug interaction with the drugs that metabolized by CYP3A4, 2E1, and 2C9. Further clinical and studies are needed to evaluate the significance of this interaction.