Ding Baodong, Ji Xiaofei, Sun Xueming, Zhang Tongtong, Mu Suping
Department of Pediatrics, Weifang Yidu Central Hospital, Weifang, China.
Weihai Songshan Community Health Service Center, Weihai, China.
Xenobiotica. 2020 Aug;50(8):913-918. doi: 10.1080/00498254.2020.1727062. Epub 2020 Feb 12.
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.
茯苓酸是一种广泛应用的具有多种药理特性的传统中药。它也存在于许多儿科常用药物中。在人肝微粒体中研究了茯苓酸对八种主要细胞色素P450（CYP）同工酶活性的影响。使用人肝微粒体（HLMs）研究了茯苓酸对八种人肝CYP同工酶（即1A2、3A4、2A6、2E1、2D6、2C9、2C19和2C8）的影响，并计算了酶动力学参数。茯苓酸以浓度依赖性方式抑制CP3A4、2E1和2C9的活性，其半数抑制浓度（IC50）值分别为15.04、27.95和24.22μM。茯苓酸是CYP3A4的非竞争性抑制剂，其IC50值为6.47μM。而对CYP2E1和2C9的抑制是以竞争性方式进行的，其IC50值分别为11.96和10.94μM。此外，茯苓酸对CYP3A4的抑制呈时间依赖性，其抑制常数（Ki）/最大反应速率抑制常数（Kis）值为7.77/0.048minμM。茯苓酸对CYP3A4、2E1和2C9活性的抑制作用表明其与由CYP3A4、2E1和2C9代谢的药物存在潜在的药物相互作用。需要进一步的临床和研究来评估这种相互作用的重要性。
