The Study On The Relationship Of Pharmackoingcs And Pharamacodynamics For Stains In Hyperlipidema Model In Rats

Many good promising drugs were to be eliminated in preclinical Phase beacuse of pharmacokinetics,so the early evaluation and forecast are necessary for pharmacokinetics and pharmacodynamics CPK—PD in preclinical Phase research,andto forecast the pharmacokinetics base to bioMarke~such as to assessment the difference between the therapeutics and the comfort on the basis of therapeutics data,which is necessary for research of new drugs.Bases on these datas excluding drug molecules datas in vitro,animal datas,individual heredity background,disease—related molecular biology data,the relationship between molecular structure of compound and pharmacodynamic,P450 enzymes and drug metabolism enzyme genotype and phenotype—the correlationbetween these and pharmacokinetic , the correlation of blood drug level and clinical responses.The translational medicine mathematical model was established to predict series of compounds in vivo pharmacokinetic—pharmacodynamic properties in drug research development and application.In the treatment ofhyperlipidemia,statins are the first choice in Lipid—lowering . Some of the adverse muscle(such as myopathy and rhabdomyolysis)reactions are rare when drug administration according at standard dose;With the development of disease,the dose change was company,and the adverse reactions also show some degree of correlations.This risk is differ in different statins,and even higher at hi曲er dose and the drug interactions exist.In this paper the prediction model was successfully established upon the drug exposure level(especially in the typical parameter-AUC)in hyperlipidemic rats.The prediction model has a good linear relationship in the range ofAUC(0—10.96multiple), Y=0.0843X+7.5956 (r2=0.9477),it could be efficacily used to predicted the relationship between triglyceride levels of TG(an important indicator of hyperlipidemia)and the drug exposure.The biggest advantage of this model is to successfully to predict the pharmacodynamics in the base of pharmacokinetic data,SO researchers could more quickly decide the research processes,requirement for dosage forms,common dose,the differences between individuals and groups,and also could be decide the value of further research and development,SO tohave a guide to the formulation development. Further more,optimization of treatment in clinical is possible if we have future study and perfect it,and also could evaluate the potential risks and benefits.