辛伐他汀对厄贝沙坦药代动力学影响的研究

The influence of simvastatin on the pharmacokinetics of irbesartan in rabbits

目的探讨辛伐他汀相同剂量(5 mg·kg-1)诱导不同时间(3 d和5 d)对新西兰大白兔体内厄贝沙坦药代动力学的影响。方法 24只新西兰大白兔随机分为4组,分别是:3 d对照组(以2%羧甲基纤维素溶液为对照,单用厄贝沙坦50 mg·kg-1)、5 d对照组(以2%羧甲基纤维素溶液为对照,单用厄贝沙坦50 mg·kg-1)、辛伐他汀3 d和辛伐他汀5d诱导组。采用HPLC-荧光法测定血药浓度,DAS3.0软件进行数据处理,计算药代动力学参数。Cmax和Tmax为实验测得。主要药代动力学参数用SPSS13.0软件包进行统计分析。结果经统计分析,与相应对照组比较,辛伐他汀3 d诱导组厄贝沙坦在兔体内的主要药代参数如AUC、CL、Cmax、T 12等差异无显著性(P>0.05);而辛伐他汀5 d诱导组的主要药代参数AUC(0-36)、AUC(0-∞)、MRT(0-36)、MRT(0-∞)、Cmax明显增加(P<0.05),CL明显降低(P<0.05);辛伐他汀5 d诱导组与辛伐他汀3 d诱导组相比,其主要药代参数AUC(0-36)、AUC(0-∞)、MRT(0-36)、MRT(0-∞)、Cmax增加(P<0.05),CL降低(P<0.05)。结论辛伐他汀诱导3 d对新西兰大白兔体内厄贝沙坦的药代动力学无影响;辛伐他汀诱导5 d明显影响新西兰大白兔体内厄贝沙坦的药代动力学;与辛伐他汀3 d诱导组比,辛伐他汀5 d诱导对新西兰大白兔体内厄贝沙坦的药代动力学影响明显。

Aim To investigate the effect of simvastatin on pharmacokinetics of irbesartan after oral administration of simvastatin 5 mg·kg-1 for 3 days and 5 days respectively.Methods 24 New Zealand white rabbits were divided into 4 groups,randomized as follows：control（3 days）,control（5 days）,simvastatin for 3 days group and simvastatin for 5 days group.The concentrations of irbesartan were determined by HPLC-fluorescence method.The results of the plasma samples were analysed with the DAS version 3.0（Bontz Inc.,Beijing,China） program to determine the compartment models and the pharmacokinetic parameters,and the statistics were analysed by SPSS 13.0 program.Results Compared with the correspond control,there was no obvious influence on the pharmacokinetic parameters of irbesartan such as AUC,CL,Cmax,T1 2 et al.（P0.05） after inducing with simvastatin（5 mg·kg-1） for 3 days;compared with the correspond control,inducing with simvastatin（5 mg·kg-1） for 5 days,the major pharmacokinetic parameters such as AUC（0-36）,AUC（0-∞）,MRT（0-36）,MRT（0-∞）,Cmax were increased obviously（P0.05）,and CL decreased obviously（P0.05）;simvastatin inducing for 5 days compared with simvastatin inducing for 3 days,the major pharmacokinetic parameters such as AUC（0-36）,AUC（0-∞）,MRT（0-36）,MRT（0-∞）,Cmax were increased obviously（P0.05）,and CL decreased obviously（P0.05）.Conclusions There is no significant influence on the pharmacokinetics of irbesartan after inducing with simvastatin（5 mg·kg-1） for 3 days.There is significant influence on the pharmacokinetics of irbesartan after inducing with simvastatin（5 mg·kg-1） for 5 days.Simvastatin（5 mg·kg-1） inducing for 5 days compared with simvastatin（5 mg·kg-1） inducing for 3 days,there is significant influence on the pharmacokinetics of irbesartan.