Explore The Relationship Between Pharmacokinetics And Pharmacodynamics For Three Statins In Hyperlipidemic Rabbits

Objectives: Investigating the relationships between the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterin(LDL-C) and the level of exposure(pharmacokinetic parameters AUC) in hyperlipidemic rabbits, which were treated byFluvastatin(FVS), Atorvastatin(AVS) and Simvasatin(SVS) with different doses. Methods：These rabbits were randomly divided into five groups:Solvent Control(SC), FVS, AVS, SVSand Nomal Control(NC). Rabbits were treated by relative statins through Gastric perfusionmethod for3weeks, as well as the SC and NC were given the same volume of distilled water.Biochemical indexes were measured in different experimental phase. Established the liquidchromatography-mass spectrometry (LC-MS) method for determining the concentration ofthree statins in rabbit plasma. Determining the PK of the first and last time after continuousadministration, calculating the pharmacokinetic-pharmacodynamics (PK-PD value). At last,taking correlation analysis. Results: AUC of the three drugs change significantly aftercontinuous administration; In the FVS, there was a linear relationship between the TC, TG,LDL-C and the AUC(R2>0.85); And in the AVS, there was a linear relationship between theTC and AUC both. Conclusion: The three statins accumulating significantly after continuousadministration, which implied there is a correlationship between the effect and the AUCaccumulation; In the FVS and AVS, there are a good linear relationship TC and AUC, whichcan be used to predicate the pharmacodynamics based on the known pharmacokinetics data.