The influence of simvastatin on the pharmacokinetics of irbesartan in rabbits
Qing Chang · Zhongguo yaolixue tongbao · 2012
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.