Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E

Green tea has been shown to exhibit cancer-preventive activities in preclin ical studies. Its principal active components include epigallocatechin gall ate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin galla te, of which EGCG is the most abundant and possesses the most potent antiox idative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose ad ministration of EGCG and Polyphenon E (decaffeinated green tea catechin mix ture). Twenty healthy subjects (five subjects/dose level) were randomly ass igned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG co ntent). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collecte d for up to 24 h after oral administration of the study medication. Tea cat echin concentrations in plasma and urine samples were determined using high performance liquid chromatography with the coulometric electrode array dete ction system, After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22. 5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min.mug/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively, E GC and EC were not detected in plasma after EGCG administration and were pr esent at low/undetectable levels after Polyphenon E administration. High co ncentrations of EGC and EC glucuronide/sulfate conjugates were found in pla sma and urine samples after Polyphenon E administration, There were no sign ificant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (C-max) of EGCG after the 800-mg dose of EGCG were found to be significantly highe r than those after the 200- and 400-mg dose. The AUC and C-max of EGCG afte r the 800-mg dose of Polyphenon E were significantly higher than those afte r the three lower doses. We conclude that the two catechin Formulations res ulted in similar plasma EGCG levels. EGC and EC were present in the body af ter the Polyphenon E administration; however, they were present predominant ly in conjugated forms. The systemic availability of EGCG increased at high er doses, possibly due to saturable presystemic elimination of orally admin istered green tea polyphenols.