Study on the pharmacokinetics of tea polyphenols injection in rat plasma

Objective To study pharmacokinetics of the main active ingredients(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG)of tea polyphenols(TP)injection in rats.Methods EGCG and ECG in rat plasma were analyzed by reversed-phase HPLC,by which EGCG and ECG were eluted from a Kromasil C18 column with a linear gradient mobile phase consisting of CH3CN-0.1% citric acid at a gradient flow rate of 1.0-1.5 mL·min-1 and monitored at a wavelength of 280 nm.Fifteen rats were randomly divided into 3 groups of 5 animals receiving iv administration of TP injection,formulated with catechins-containing extract from green tea,at doses of 150,100 and 50 mg·kg-1,respectively.Blood samples were collected pre-dosing and 2,5,10,20,40,60,90,120,180,240,300 min postdosing.Aliquots of obtained plasma(200 μL)were cleaned up by liquid-liquid extraction with double volumes of EtoAc and were reconstituted with 100 μL of 10% CH3CN aqueous solution before injecting to chromatograph.Results The time course of EGCG and ECG concentrations in rat plasma decayed in a biexponential fashion.Their iv pharmacokinetics could be described by the two-compartment model and first-order kinetics with t1/2β 112.39-145.20 min and 46.63-61.48 min,Vd 6.28-7.96 L·kg-1 and 0.90-1.22 L·kg-1,CL 0.034-0.044 L·kg-1·min-1 and 0.010-0.015 L·kg-1·min-1 for EGCG and ECG,respectively.Conclusions The EGCG and ECG in plasma of rats administered i.v.TP injection pharmacokinetically behaved with linear kinetics over dose range studied.The two catechin derivatives undergo rapid elimination from rat body.As compared with ECG,EGCG eliminates at a relatively slow rate,and is distributed very widely with a Vd greatly exceeding the volume of total body water,suggesting that EGCG is likely to enter the tissue cells or strongly bind to some tissues to exert its potent antioxidant effects.The aforementioned characteristics of EGCG may be due to its high lipophilicity.