Studies Of The Relationship Of Pharmacodynamics And Pharmacokinetics Of Calenduloside E

[Objective]To study the relationship of pharmacodynamic(PD) and pharmacokinetie(PK) of CE,to explore new sorts of traditional Chinese medicine of high standard to provide a rational guidance for the clinical treatment,and to offer an example for PK/PD research.[Methods]Deeply studied the antiarrhythmic effect of CE by the method of ligating the left anterior descending branch of rats,bringing out arrhythmy in rats by Aco and in cavy by Oua.Determined the metabolism of CE after biotransformation of Liver enzyme drugs by rat liver microsomal incubation,and then determined the metabolism by high performance liquid chromatographic method(RP-HPLC).Upon this we definited the aim compound in the catabolism of CE in rats.By examining the concentration in main organs and in their excrement at different intervals by RP-HPLC,we primarily comprehend the tissue distribution and excretion of Calenduloside E in rats' main organs after received orally.[Results]1.The 3 groups of CE(15.00,7.50,3.75mg/kg )as well as the positive control group(Amiodarone Hydrochloride 160mg/kg)could prelong the latent period of arrhythmy caused by ligating the left anterior descending branch of rats,significantly shorten the lasting time of arrhythmy within 30min,and obviously reduce the oceuranee of IVF.Groups of CE7.50 mg/kg and the positive control group (lidocaine7mg/kg) recovered the ECM of arrhythmy rats caused by Aco within 2h both to 100%.The 3 CE groups(13.00,6.50,3.25mg/kg)and the positive control group (Amiodarone Hydrochloride 139.2mg/kg) both could increase the usage of Oua which caused VP,VT,VF,CA in cavy.2.CE remained its structure and acted on the organism in the original form after catabolism by Liver enzyme drugs.3.CE gradually distributed over main orgins as soon as absorbed through gastrointestinal tract.Only 20min later it spreaded in liver,and was examined in the heart as target organ after 60min,remaining for as long as 4 hours,and reached its peak at 2h.In kidney saw the delay of examination,which coincided with the regular pattern of tissue distribution in pharmacokineti.It was not found in other organs and tissues such as brain,lungs,spleen,muscles and sex glands.The level of CE determined at different intervals in samples of bile,urine and feces altered regularly.[Conclusion]CE lead a significant resist effect towards the arrhythmy in rats caused by Aco or by ligating the left anterior descending branch,and in cavy caused by Oua.It remained its structure as original form after catabolism by Liver enzyme drugs.CE distributed over main orgins when received orally,remaining in the heart for as long as 4 hours,and excreted through biles and urine in the forms of feces and urine.There are closely relationship and regulary in pharmacodynamic and pharmacokineti.