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目的:探索附子配伍干姜对附子主要成分乌头类生物碱的代谢酶亚型CYP1A2和CYP3A4酶活性的影响。方法:通过采用“Cocktail”探针药物法,利用特异性探针底物咖啡因和咪达唑仑,建立同时测定两种探针药物血药浓度的高效液相色谱方法,并计算其药动学参数,评价两种代谢酶活性。结果:干姜组与对照组比较,咖啡因的主要药动学参数t1/2β、AUC、CL和K10均没有显著性差异(P>0.05),表明干姜组对CYP1A2酶活性无影响;咪达唑仑的主要药动学参数t1/2β和AUC增大,CL和K10降低,且都具有显著性差异(P<0.05),表明干姜组能够抑制CYP3A4酶活性。附子干姜组与对照组比较,咖啡因和咪达唑仑的主要药动学参数t1/2β、AUC、CL和K10均无统计学差异(P>0.05)。结论:干姜组对CYP3A4酶具有抑制作用,能够减慢附子中主要药效成分乌头类生物碱在体内的代谢,因此,从代谢酶的角度可以阐明姜附配伍,能够增强附子的药效。
Objective: To explore the effects of aconite and dried ginger on the activities of the enzymes CYP1A2 and CYP3A4 of aconite alkaloids, the main constituents of aconite. Methods: By using the “Cocktail” probe drug method, the specific probe substrate caffeine and midazolam were used to establish a HPLC method for simultaneous determination of plasma concentrations of two probe drugs. Pharmacokinetic parameters, evaluation of two metabolic enzyme activities. Results: Compared with the control group, there was no significant difference in the main pharmacokinetic parameters t1 / 2β, AUC, CL and K10 between the ginger group and the control group (P> 0.05), indicating that the ginger group had no effect on the CYP1A2 enzyme activity; The main pharmacokinetic parameters t1 / 2β and AUC of azaconitine and CL and K10 decreased significantly (P <0.05), indicating that ginger ginger group can inhibit CYP3A4 activity. There was no significant difference in the main pharmacokinetic parameters t1 / 2β, AUC, CL and K10 of caffeine and midazolam between aconite and ginger group (P> 0.05). Conclusion: Ginger group can inhibit the activity of CYP3A4 enzyme and slow down the metabolism of aconite alkaloid, the major active ingredient of aconite. Therefore, it is possible to elucidate the compatibility of aconite and alkaloids from the perspective of metabolic enzymes, and enhance the efficacy of aconite .