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目的:研究复方丹参注射液对大鼠肝脏细胞色素(cytochrome,CY)P450酶不同亚型活性的影响。方法:大鼠随机分为复方丹参注射液高剂量组、中剂量组、低剂量组和对照组。采用反相高效液相色谱(RT-HPLC)测定探针药物在血浆中的质量浓度,利用3P97药动学软件分析数据,计算药动学参数。结果:与对照组比较,复方丹参注射液高剂量组可使咖啡因的消除半衰期(t1/2β)由50.492 min升至54.456 min,药时曲线下面积(AUC)明显升高,清除率(CL)明显降低;高剂量组可缩短氯唑沙宗的t1/2β,降低AUC,显著增加CL;咖啡因和氯唑沙宗的中、低剂量组主要药动学参数无统计学差异;随着给药剂量的增加,甲苯磺丁脲的t1/2β,AUC逐渐增大,CL逐渐降低;而复方丹参注射液各组对咪达唑仑的药动学参数无显著性差异。结论:复方丹参注射液对CYP2C9具有一定的抑制作用,且呈剂量依赖型;复方丹参注射液高剂量组对CYP1A2有较弱的抑制作用,对CYP2E1有较弱的诱导作用,而复方丹参注射液中、低剂量组对CYP1A2和CYP2E1均无影响;复方丹参注射液高、中、低剂量组对CYP3A4的活性无影响。
Objective: To study the effect of Fufang Danshen injection on the activities of liver cytochrome P450 enzymes in different subtypes. Methods: The rats were randomly divided into high-dose group, middle-dose group, low-dose group and control group. The concentration of probe drug in plasma was determined by reverse-phase high performance liquid chromatography (RT-HPLC). The pharmacokinetic parameters were calculated by 3P97 pharmacokinetic software. Results: Compared with the control group, the half-life of elimination (t1 / 2β) of caffeine was increased from 50.492 to 54.456 min in the high-dose Danshen injection group. The area under the curve (AUC) ) Was significantly lower; high-dose group can shorten the t1 / 2β of chlorzoxazone, reduce AUC, significantly increased CL; caffeine and chlorzoxazone in the low-dose group of the main pharmacokinetic parameters were not statistically different; with Tolbutamide’s t1 / 2β, AUC gradually increased and CL decreased gradually with the increase of the dosage. There was no significant difference in the pharmacokinetic parameters of midazolam in each group. Conclusion: Salvia miltiorrhiza injection has certain inhibitory effect on CYP2C9 in a dose-dependent manner. High-dose compound Salvia miltiorrhiza injection has a weaker inhibitory effect on CYP1A2 and a weaker induction effect on CYP2E1, while compound Danshen injection Medium and low dose groups had no effect on CYP1A2 and CYP2E1; high, medium and low dose Fufang Danshen injection group had no effect on CYP3A4 activity.