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目的采用Cocktail探针药物法评价威麦宁胶囊对大鼠体内6种CYP450亚型酶活性的影响。方法分别选用甲苯磺丁脲、氯唑沙宗、茶碱、咪达唑仑、奥美拉唑和右美沙芬作为CYP2C6、CYP2E1、CYP1A2、CYP3A2、CYP2D1和CYP2D2的探针底物。大鼠每日灌胃威麦宁胶囊1.6 g·kg-1,采用LC-MS/MS测定给药前后大鼠体内6种混合探针的血药浓度,计算药动学参数。结果威麦宁胶囊连续给药2周后,与给药前相比,奥美拉唑ρmax、AUC0-t、tmax及AUC0-∞显著升高(P<0.05);咪达唑仑ρmax、AUC0-t和AUC0-∞显著升高(P<0.01或P<0.05);右美沙芬ρmax、AUC0-t升高(P<0.05);甲苯磺丁脲t1/2、AUC0-∞和tmax显著升高(P<0.01或P<0.05),而CL/F显著降低(P<0.01),ρmax、AUC0-t无显著改变(P>0.05);氯唑沙宗ρmax升高(P<0.05),CL/F降低(P<0.05),AUC0-t升高但无显著差异(P>0.05);茶碱ρmax、AUC0-t升高但无显著差异(P>0.05)。表明奥美拉唑、咪达唑仑和右美沙芬代谢明显减慢(均P<0.05),茶碱、甲苯磺丁脲、氯唑沙宗的代谢无显著差异;威麦宁胶囊对大鼠体内CYP2D1、CYP3A2、CYP2D2酶有抑制作用,对CYP1A2、CYP2C6、CYP2E1酶的活性无显著影响。结论当威麦宁胶囊与CYP2C19、CYP3A4、CYP2D6酶的底物药物合用时,需要调整给药剂量,避免因药物相互作用使体内血药浓度过高产生毒副作用。
Objective To evaluate the effects of Weimaining capsules on the activities of six CYP450 subtypes in rats using the Cocktail probe method. Methods Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were selected as probe substrates for CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 respectively. Rats were fed with Weimaining capsule 1.6 g · kg-1 daily. The plasma concentrations of 6 kinds of mixed probes in rats before and after administration were determined by LC-MS / MS, and the pharmacokinetic parameters were calculated. Results Weimainen capsules were significantly increased (P <0.05) two weeks after continuous administration of omeprazole ρmax, AUC0-t, tmax and AUC0-∞, midazolam ρmax, AUC0 (P <0.01 or P <0.05), pmax and AUC0-t of dextromethorphan increased significantly (P <0.05), and the tolbutamide t1 / 2, AUC0-∞ and tmax increased significantly (P <0.01 or P <0.05), while CL / F decreased significantly (P <0.01), while pmax and AUC0-t had no significant change (P> 0.05) CL / F (P <0.05), AUC0-t increased but no significant difference (P> 0.05). The theophylline ρmax and AUC0-t increased but no significant difference (P> 0.05). Metoprolol, midazolam and dextromethorphan metabolism was significantly slowed (all P <0.05), theophylline, tolbutamide, and chlorzoxazone metabolism was no significant difference; Wei Maening capsule on rats In vivo CYP2D1, CYP3A2, CYP2D2 enzyme inhibition, CYP1A2, CYP2C6, CYP2E1 enzyme activity was not significantly affected. Conclusion When Weimaining Capsules and CYP2C19, CYP3A4, CYP2D6 enzyme substrate drugs, the need to adjust the dose to avoid drug interactions so that the blood concentration in the body produces toxic and side effects.