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目的考察斑蝥酸钠维生素B_6和复方苦参注射液对人肝微粒体细胞色素P450酶(CYP450)7种同工酶活性的体外抑制作用。方法将66.70%,33.40%,16.70%,6.67%,2.22%,7.41‰,2.47‰浓度的斑蝥酸钠维生素B_6和100.00%,50.00%,25.00%,10.00%,3.33%,1.11%,3.70‰复方苦参注射液分别与人肝微粒体进行孵育,以非那西丁、双氯芬酸、(S)-美芬妥英、右美沙芬、咪达唑仑、安非他酮、阿莫地喹分别作为CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP3A4、CYP2B_6、CYP2C8的探针底物,用LC-MS/MS检测探针底物代谢物的生成量,计算半数抑制浓度(IC_(50))。结果斑蝥酸钠维生素B_6注射液对CYP450亚型活性的IC_(50)>10 mg,远高于其日用药量(0.1~0.5 mg)。复方苦参注射液对CYP1A2和CYP2D6的IC_(50)值分别是15.2,10.3 mL,均小于其日用药量(20mL);对CYP2C8和2C19的IC_(50)值均为21.1 mL,均接近其日用药量;对CYP2B_6、2C9、3A4-M和3A4-T的IC_(50)值分别为63.5,72.0,95.5,92.5 mL,均远高于其日用药量(20 mL)。结论临床剂量下,斑蝥酸钠维生素B_6注射液在体外对CYP450亚型活性无影响;复方苦参注射液在体外对CYP1A2和CYP2D6均有明显的抑制作用,对2C8和2C19均有一定程度的抑制作用,对CYP2B_6、2C9、3A4-M和3A4-T均无明显的抑制作用。临床静脉用复方苦参注射液时,应注意可能因CYP450酶抑制引起的药物相互作用。
Objective To investigate the inhibitory effects of sodium cantharidate vitamin B 6 and compound kushen injection on the activities of 7 isoenzymes of human liver microsomal cytochrome P450 enzyme (CYP450) in vitro. Methods Sodium cantharidin vitamin B_6 with concentration of 66.70%, 33.40%, 16.70%, 6.67%, 2.22%, 7.41% and 2.47% Compound matrine injection were incubated with human liver microsomes, respectively, phenacetin, diclofenac, (S) - mephenytoin, dextromethorphan, midazolam, bupropion, amodiaquine respectively The half-inhibitory concentration (IC 50) was calculated as the substrate yield of the probe substrate by LC-MS / MS as a probe substrate for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2B_6 and CYP2C8. Results The IC50 (50)> 10 mg of sodium cantharidate vitamin B_6 injection on CYP450 subtype was much higher than the daily dosage (0.1 ~ 0.5 mg). The IC 50 value of compound Kushen injection for CYP1A2 and CYP2D6 were 15.2 and 10.3 mL, respectively, which were less than the daily dosage (20 mL). The IC 50 values of CYP2C8 and 2C19 were both 21.1 mL, The daily dose of IC50 of CYP2B_6, 2C9, 3A4-M and 3A4-T were 63.5, 72.0, 95.5 and 92.5 mL, respectively, much higher than their daily dose of 20 mL. Conclusions Sodium cantharidin vitamin B 6 injection has no effect on CYP450 subtype activity in vitro. Compound Kushen injection has significant inhibitory effect on CYP1A2 and CYP2D6 in vitro, and inhibits both CYP4A and 2C19 to a certain extent CYP2B_6, 2C9, 3A4-M and 3A4-T had no significant inhibitory effect. Clinical intravenous Compound Kushen injection, should pay attention to possible drug interactions caused by inhibition of CYP450 enzyme.