Department of Pharmacy, People's Hospital of Rizhao, Rizhao, China.
Department of Pediatrics, People's Hospital of Rizhao, Rizhao, China.
Pharm Biol. 2021 Dec;59(1):532-536. doi: 10.1080/13880209.2021.1917630.
Pogostone possesses various pharmacological activities, which makes it widely used in the clinic. Its effect on the activity of cytochrome P450 enzymes (CYP450s) could guide its clinical combination.
To investigate the effect of pogostone on the activity of human CYP450s.
The effect of pogostone on the activity of CYP450s was evaluated in human liver microsomes (HLMs) compared with blank HLMs (negative control) and specific inhibitors (positive control). The corresponding parameters were obtained with 0-100 μM pogostone and various concentrations of substrates.
Pogostone was found to inhibit the activity of CYP3A4, 2C9, and 2E1 with the IC values of 11.41, 12.11, and 14.90 μM, respectively. The inhibition of CYP3A4 by pogostone was revealed to be performed in a non-competitive and time-dependent manner with the value of 5.69 μM and the KI/K value of 5.86/0.056/(μM/min). For the inhibition of CYP2C9 and 2E1, pogostone acted as a competitive inhibitor with the value of 6.46 and 7.67 μM and was not affected by the incubation time.
The inhibitory effect of pogostone on the activity of CYP3A4, 2C9, and 2E1 has been disclosed in this study, implying the potential risk during the co-administration of pogostone and drugs metabolized by these CYP450s. The study design provides a reference for further investigations to validate the potential interaction.
莪术酮具有多种药理活性，因此在临床上得到广泛应用。其对细胞色素 P450 酶（CYP450s）活性的影响可指导其临床联合用药。
研究莪术酮对人细胞色素 CYP450s 活性的影响。
用人肝微粒体（HLMs）与空白 HLMs（阴性对照）和特异性抑制剂（阳性对照）比较，评价莪术酮对 CYP450s 活性的影响。用 0-100 μM 莪术酮和不同浓度的底物获得相应的参数。
莪术酮被发现能抑制 CYP3A4、2C9 和 2E1 的活性，IC 值分别为 11.41、12.11 和 14.90 μM。莪术酮对 CYP3A4 的抑制呈非竞争和时间依赖性，值为 5.69 μM，KI/K 值为 5.86/0.056/（μM/min）。对于 CYP2C9 和 2E1 的抑制，莪术酮为竞争性抑制剂，值为 6.46 和 7.67 μM，不受孵育时间的影响。
本研究揭示了莪术酮对 CYP3A4、2C9 和 2E1 活性的抑制作用，提示在莪术酮与这些 CYP450 代谢的药物联合使用时存在潜在风险。该研究设计为进一步验证潜在相互作用的研究提供了参考。
