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目的:考察CYP2C9抑制剂胺碘酮对艾瑞昔布在大鼠体内药动学的影响。方法:40只健康雄性SD大鼠随机分为2组(n=20),实验组连续7 d灌胃胺碘酮灌胃液(40 mg·kg~(-1),qd),对照组灌胃等量空白灌胃液。2组均于第8天单次灌胃艾瑞昔布灌胃液20 mg·kg~(-1),按确定时间点取血,LC-MS/MS法测定艾瑞昔布血药浓度,DAS 2.1.1软件拟合药时曲线并计算药动学参数,SPSS 13.0软件进行统计学分析。结果:实验组和对照组的主要药动学参数如下:AUC0-24 h分别为(1 814.8±693.4)ng·h·mL~(-1)和(1 125.1±457.6)ng·h·mL~(-1);AUC0-∞分别为(2 091.6±887.1)ng·h·mL~(-1)和(1 331.3±592.6)ng·h·mL~(-1);t1/2分别为(7.8±4.5)h和(7.4±3.8)h;tmax分别为(1.7±0.6)h和(1.46±0.60)h;CL分别为(0.01±0.01)L·h~(-1)·kg~(-1)和(0.02±0.01)L·h~(-1)·kg~(-1);V分别为(0.11±0.05)L·kg~(-1)和(0.17±0.07)L·kg~(-1);Cmax分别为(268.2±115.7)ng·mL~(-1)和(162.2±53.0)ng·mL~(-1)。与对照组相比,实验组大鼠的AUC0-24 h、AUC0-∞、Cmax显著增大(P<0.05),V、CL显著减小(P<0.05),其他参数差异无统计学意义(P>0.05)。结论:CYP2C9抑制剂(胺碘酮)对艾瑞昔布在大鼠体内的药动学产生影响。
Objective: To investigate the effect of CYP2C9 inhibitor amiodarone on the pharmacokinetics of erecT in rats. Methods: Forty healthy male Sprague-Dawley rats were randomly divided into 2 groups (n = 20). The experimental group was given gastric lavage of amiodarone (40 mg · kg -1, qd) for 7 consecutive days, Equal amount of blank irrigation fluid. The rats in both groups were given intragastric administration of irrecoxib 20 mg · kg -1 orally on the 8th day, and blood was collected at the determined time points. The plasma concentration of irisoxib was measured by LC-MS / MS, DAS 2.1.1 software fitting drug curve and calculate the pharmacokinetic parameters, SPSS 13.0 software for statistical analysis. RESULTS: The main pharmacokinetic parameters of experimental group and control group were as follows: AUC0-24 h were (1 814.8 ± 693.4) ng · h · mL -1 and (1 125.1 ± 457.6) ng · h · mL ~ (-1); AUC0-∞ were (2901.6 ± 887.1) ng · h · mL -1 and (1 331.3 ± 592.6) ng · h · mL -1, respectively; t1 / 2 was 7.8 ± 4.5 h and 7.4 ± 3.8 h respectively; tmax was (1.7 ± 0.6) h and (1.46 ± 0.60) h respectively; CL was (0.01 ± 0.01) L · h -1 · kg ~ (0.11 ± 0.05) L · kg -1 and (0.17 ± 0.07) L · kg -1, respectively, and (0.02 ± 0.01) L · h -1 · kg -1 ~ (-1); Cmax were (268.2 ± 115.7) ng · mL -1 and (162.2 ± 53.0) ng · mL -1, respectively. Compared with the control group, the AUC0-24 h, AUC0-∞ and Cmax in experimental group were significantly increased (P <0.05), V and CL were significantly decreased (P <0.05), and the other parameters were not statistically different P> 0.05). CONCLUSIONS: CYP2C9 inhibitor (amiodarone) has an effect on the pharmacokinetics of erecterodine in rats.