The Study Of Pharmacokinetics Of3,5,4’-tri-O-acetylresveratrol And Resveratrol In SD Rats

3,5,4’-tri-O-acetylresveratrol is a prodrug of resveratrol. Resveratrol [(E)-3,5,4’-trihydroxy-trans-stilbene] is a polyphenolic compound which has substantial pharmacological activities, such as cardio-protection, liver protection, radiation protection, anti-cancer, anti-oxidation, anti-ageing and neuro-protection. This study aims at studying and comparing the pharmacokinetics between3,5,4’-tri-O-acetylresveratrol and resveratrol, clarifying the process and properties of ADME and calculating pharmacokinetic parameters.I Synthesize3,5,4’-tri-O-acetylresveratrol3,5,4’-tri-O-acetylresveratrol was synthesized from resveratrol and acetification by heating and refluxing. The reaction was only one step, the chemical yield was87.7%, and the purity was over99.0%. Ⅱ Compare pharmacokinetics between3,5,4’-tri-O-acetylresveratrol and resveratrol1The establishment of the HPLC method for the determination of resveratrol in rat plasmaSensitive and simple HPLC methods for quantitative determination of resveratrol in rat plasma, tissues, urine and feces were developed. All values of accuracy, precision and recovery were within the recommended limits.2Concentration-time curve2.1The comparative study of pharmacokinetics between3,5,4’-tri-O-acetylresveratrol and resveratrolAfter oral administration of either3,5,4’-tri-O-acetylresveratrol or resveratrol to rats at a dose of438μmol/kg (resveratrol equivalent) respectively, the concentration-time curves were analyzed through DAS2.0.3,5,4’-tri-O-acetylresveratrol showed a1.34-fold increase in half-life (t1/2) of resveratrol and a1.15-fold increase in area under curve (AUC).2.2The study of pharmacokinetics of3,5,4’-tri-O-acetylresveratrolThe concentration of resveratrol was determined at different time after ig at the dose of75mg·kg-1,150mg·kg-1,300mg·kg-13,5,4’-tri-O-acetylresveratrol respectively. The data were analyzed by DAS2.0and pharmacokinetic parameters were attained under different conditions. The results indicated that the concentration-time (C-T) curves of ig different accorded with first-order linear equation. Three curves all possess double peaks, which may be related to enterohepatic circulation, recirculation and discordant absorption. Ⅲ The study of tissue distributionAfter5,15,60min of administration of100mg·kg-1resveratrol, the concentrations of main tissues were as follows:intestine> stomach> liver> heart> lung> kidney> gonad> brain; After15,90,180min of administration of150mg·kg-13,5,4’-tri-O-acetylresveratrol, the concentrations in main tissues were as follows:intestine> stomach> lung> liver> heart> kidney> gonad> brain. The concentrations of resveratrol in brain were lowest after administration both drugs to rats. This indicated that both drugs were difficult to penetrate across the blood brain barrier. Besides, the concentrations in heart were higher than some tissues, which indicted resveratrol had affinity to heart. The difference was that the resveratrol concentration in lung after administration of3,5,4’-tri-O-acetylresveratrol was much higher than that in lung after administration of resveratrol, which was up to20folds. This indicted that3,5,4’-tri-O-acetylresveratrol targeted lung tissue to a certain degree. IV The study of excretion3,5,4’-tri-O-acetylresveratrol was given to the SD rats by gastrogavage at the dose of150mg.kg-1. The ratio of resveratrol in urine was1.69%of the total, the ratio of that in feces was0.99%, which suggested that portions of resveratrol could be eliminated by transforming into other metabolites.