瓜蒌皮注射液对人肝微粒体CYP450酶4种亚型的影响

目的研究瓜蒌皮注射液对人肝细胞色素P450(CYP450)酶4种亚型CYP1A2、CYP2B6、CYP2C9和CYP2D6的体外抑制作用。方法瓜蒌皮注射液8个不同浓度(2%、1%、0.2%、0.05%、0.01%、0.005%、0.002%、0.000 5%)的工作液分别与4种CYP450酶亚型的探针底物混合,即非那西丁(CYP1A2)、安非他酮(CYP2B6)、双氯芬酸(CYP2C9)、右美沙芬(CYP2D6),用维拉帕米作为内标,在人肝微粒体中孵育,采用高效液相色谱法检测4种探针底物的剩余浓度,计算半数抑制浓度(IC_(50))。结果瓜蒌皮注射液对CYP1A2、CYP2B6、CYP2C9和CYP2D6的IC_(50)值均大于临床常用量。结论正常用量下,瓜蒌皮注射液对人CYP450酶的4亚型无明显影响。

Effects of Gualoupi Injection on 4 subtypes of human liver CYP450

Objective To study inhibitory effects of Gualoupi Injection on 4 subtypes of human liver cytochrome P450s (CYP1A2, CYP2B6, CYP2C9, and CYP2D6). Methods Eight different doses of Gualoupi Injection (2%, 1%, 0.2%, 0.05%, 0.01%, 0.005%, 0.002%, and 0.000 5%) were incubated with human liver microsomes in 4 kinds of specific probe substrates, including phenacetin (CYP1A2), amfebutamone (CYP2B6), diclofenac (CYP2C9), and dextromethorphan (CYP2D6). Verapamil was used as internal reference to calculate other specific probe substrates. HPLC-UV method was used to analyze the residual concentration of specific probe substrates and calculate the IC₅₀ values. Results IC₅₀ values of Gualoupi Injection with CYP1A2, CYP2B6, CYP2C9, and CYP2D6 were higher than the therapeutic dose. Conclusion Gualoupi Injection might not has significant effect on 4 subtypes of human CYP450s within curing dose.