CYP2C9抑制剂对艾瑞昔布大鼠体内药动学的影响

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：AUC_{0-24 h}分别为（1 814.8±693.4） ng·h·mL^-1和（1 125.1±457.6） ng·h·mL^-1；AUC_0-∞分别为（2 091.6±887.1） ng·h·mL^-1和（1 331.3±592.6） ng·h·mL^-1；t_1/2分别为（7.8±4.5） h和（7.4±3.8） h；t_max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；C_max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AUC_{0-24 h}、AUC_0-∞、C_max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。

Effect of CYP2C9 inhibitor on the pharmacokinetics of imrecoxib in rats

OBJECTIVE To study the effect of CYP2C9 on the pharmacokinetic of imrecoxib in rats.METHODS Forty SD rats were randomly divided into two groups (n=20). Rats in the test and control group were pretreated with amiodarone (40 mg·kg^-1) and blank solution for consecutively 7 days (qd), respectively. On day 8,each rat was intragastrically administered with imrecoxib (20 mg·kg^-1). Blood samples from plexus venous at fundus oculiwere were collected at fixed time and tested. The pharmacokinetics were calculated with DAS 2.1.1 software and analyzed with SPSS 13.0 software.RESULTS The main pharmacokinetic parameters of test group and control group were as follows:AUC_{0-24 h} was (1 814.8±693.4) ng·h·mL^-1 and (1 125.1±457.6) ng·h·mL^-1; AUC_0-∞ (2 091.6±887.1) ng·h·mL^-1 and (1 331.3±592.6) ng·h·mL^-1; t_1/2 (7.8±4.5) h and (7.4±3.8) h; t_max (1.7±0.6) h and (1.46±0.60) h; CL (0.01±0.01) L·h^-1·kg^-1 and (0.02±0.01) L·h^-1·kg^-1; V (0.11±0.05) L·kg^-1 and (0.17±0.07) L·kg^-1; C_max (268.2±115.7) ng·mL^-1 and (162.2±53.0) ng·mL^-1. Compared with control group, the main pharmacokinetics including AUC_{0-24 h}, AUC_0-∞ and C_max increased significantly (P<0.05), and V and CL decreased significantly (P<0.05). However, the difference in other pharmacokinetics showed no statistical significance (P>0.05).CONCLUSION Amiodarone, an inhibitor of CYP2C9, has significant effect on the pharmacokinetic of imrecoxib in rat.