Pharmacokinetics Of Thealfavin-3,3’-digallate In Rats

TFs have attracted many researchers in recent years, because of its various physiological activities and medical function. There have been many reports on the study of TFs’s pharmacological effects, however, the research report about its monomer reactivity has hardly been met, and there are little relevant literatures published domestically and abroad about researches on pharmacokinetics of TFs, let alone pharmacokinetic analysis. In order to promote the development of TFs, the Pharmacokinetic process of TFDG in rats was systematically studied in this paper. The main conclusions are shown as below:(1) Isolation and Purification of TFDG.:The purification of TFs was conducted with macroporous resin, using60%of ethanol as eluant. TFs were obtained with a purity of85%and yield about25%. Purifying TFDG with polyamide, the solvent system including methanol, chloroform and acetone with their respective ratio as5:5:8; concentration of sample solution1.25g/100mL with a flow rate of2mL/min, collected at designated intervals. Isocratic elution TFDG with a purity of94.40%was obtained, the yield of TFDG was16.30%.(2) Plasma Pharmacokinetics of TFDG in Rats:Using HPLC-PDAto determination of TFDG in rat plasma samples. The method is specific and accurate, the impurity peak and TFDG in plasma were separated on baseline. The standard curve has good linearity over the range of0.25～20μg/mL for TFDG, with weighed linear regression equation of Y (peak area ratio of analyst/IS)=18936X (analyst concentration, μg/mL)-277.17,(Rz=0.9988, n=3). The intra-and inter-day precision (R.S.D.), obtained by measuring QC samples at high, middle and low concentrations in a set of5replicates on a single assay day and5separate days, were better than6.80%, and the average accuracy, expressed as relative recovery calculated based on linear regression equation of standard curve, was between103.12%～106.42%. The extraction recovery of TFDG was75.52%～83.33%. The plasma samples were stable for at least30days at-20℃and24h at room temperature. The Cmax of TFDG in rat plasma after iv(Intravenous injection) administration (different concentrates,25mg/kg,50mg/kg and100mg/kg) was reached at2nd hour, then gradually decreased, very limited amounts of TFDG was detected in plasma after10h. The PK behavior of TFDG in rat plasma could be described by non-linear kinetics, the AUC changes along with the dose of TFDG, but not in proportion to it. The CL and Vd had obviously changed. It also showed that TFDG distribute widely in rats with a long half-life, and can play an important role within the cells.(3) Tissue Distribution of TFDG in Rats:Using HPLC-PDA to determination of TFDG in rat kidney, heart, liver and brain tissues. The method is specific and accurate. The impurity peak and TFDG in tissues were separated on baseline. The standard curve had good linearity over the range of0.25～20μg/mL for TFDG, the LOQ was0.25μg/mL(S/N=3). The intra-and inter-day precision (R.S.D.) were better than10%. The tissues samples were stable for at least30days at-20℃and6h at room temperature. When50mg/kg of TFDG was administered iv to rats, TFDG was rapidly distributed into each tissue, and brain tissue exhibited the highest exposure, followed by kidney liver and heart. However, the content of TFDG in tissues was far lower than that in plasma, which indicated that the bioavailability of TFDG is extremely low, only little TFDG had get into the tissues.