Clinical and pre-clinical pharmacokinetics of green tea polyphenols

摘要

Tea consumption has been suggested to have beneficial effects for human health, especially in cancer prevention. At present, epidemiological evidence of the protective effect of tea consumption against the development of human cancer is not conclusive. Interpretation of epidemiological data and extrapolation of rodent data to humans are generally hampered by inadequate information on the bioavailability and pharmacokinetics of tea constituents. We have performed studies to determine the pharmacokinetics of green tea in humans after single and multiple oral dose administration of tea polyphenols and the contribution of hepatic first-pass elimination to the low oral bioavailability of green tea catechins in animals. EGCG was present in the systemic blood in the unchanged form in humans after oral administration of two green tea polyphenol products, EGCG and Polyphenon E (a mixture of major green tea polyphenols). Oral administration of EGCG and Polyphenon E resulted in similar systemic exposure of EGCG. EGC and EC were present in glucuronic acid/sulfate conjugates in blood and urine samples after the Polyphenon E administration. Large inter-subject variations in the systemic levels of green tea catechins were observed following oral administration of green tea polyphenols. We found that it is safe for healthy human subjects to take green tea polyphenols for four weeks in amounts equivalent to those contained in 8 to 16 cups of green tea once a day or in divided doses twice a day. Systemic availability of EGCG increased more than 60% after chronic green tea polyphenol administration at high doses once a day. Oral administration of green tea polyphenols at the selected doses and dosing schedules did not elicit overall changes in the selected pharmacodynamic measurements. Oral bioavailability of green tea catechins was demonstrated to be low in animals and possibly in humans. Based on our pre-clinical study, we found that first-pass hepatic elimination of green tea catechins didn't play a significant role in the presystemic elimination of orally administered catechins. Factors within the gastrointestinal tract such as limited membrane permeability, transporter mediated intestinal secretion, or gut wall metabolism may contribute more significantly to the low oral bioavailability of green tea catechins.