In vitro effect of pachymic acid on the activity of Cytochrome P450 enzymes

Abstract

1. 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.

2. The effect of pachymic acid on the activity of eight major CYP isoforms was investigated in human liver microsomes.

3. The effects of pachymic acid on eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs), and the enzyme kinetic parameters were calculated.

4. The activity of CP3A4, 2E1, and 2C9 was inhibited by pachymic acid in a concentration-dependent manner with IC₅₀ values of 15.04, 27.95, and 24.22 μM, respectively. Pachymic acid is a non-competitive inhibitor of CYP3A4, with the Ki value of 6.47 μM. While the inhibition of CYP2E1 and 2C9 was performed in a competitive manner, with the Ki value of 11.96 and 10.94 μM, respectively. Moreover, the inhibition of CYP3A4 was in a time-dependent manner with the K_I/K_inact value of 7.77/0.048 min⁻¹μM⁻¹.

5. The in vitro 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 in vivo studies are needed to evaluate the significance of this interaction.

Keywords:

• Pachymic acid
• cytochrome P450 enzymes
• drug-drug interaction
• CYP3A4
• CYP2E1
• CYP2C9

Disclosure statement

No potential conflict of interest was reported by the author(s).