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Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 [M-J. L., P. M., L. C., X. M., F. Y. B., C. S. Y.], and Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey 08854 [S. P., G. L., S. M., C. S. Y.]
Green tea and tea polyphenols have been studied extensively as cancer chemopreventive agents in recent years. The bioavailability and metabolic fate of tea polyphenols in humans, however, are not clearly understood. In this report, the pharmacokinetic parameters of (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) were analyzed after administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects. The plasma and urine levels of total EGCG, EGC, and EC (free plus conjugated forms) were quantified by HPLC coupled to an electrochemical detector. The plasma concentration time curves of the catechins were fitted in a one-compartment model. The maximum plasma concentrations of EGCG, EGC, and EC in the three repeated experiments with green tea were 77.9 ± 22.2, 223.4 ± 35.2, and 124.03 ± 7.86 ng/ml, respectively, and the corresponding AUC values were 508.2 ± 227, 945.4 ± 438.4, and 529.5 ± 244.4 ng·h·ml-1, respectively. The time needed to reach the peak concentrations was in the range of 1.3–1.6 h. The elimination half-lives were 3.4 ± 0.3, 1.7 ± 0.4, and 2.0 ± 0.4 h, respectively. Considerable interindividual differences and variations between repeated experiments in the pharmacokinetic parameters were noted. Significant differences in these pharmacokinetic parameters were not observed when EGCG was given in decaffeinated green tea or in pure form. In the plasma, EGCG was mostly present in the free form, whereas EGC and EC were mostly in the conjugated form. Over 90% of the total urinary EGC and EC, almost all in the conjugated forms, were excreted between 0 and 8 h. Substantial amounts of 4'-O-methyl EGC, at levels higher than EGC, were detected in the urine and plasma. The plasma level of 4'-O-methyl EGC peaked at 1.7 ± 0.5 h with a half life of 4.4 ± 1.1 h. Two ring-fission metabolites, (-)-5-(3',4',5'-trihydroxyphenyl)-
-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-valerolactone (M6), appeared in significant amounts after 3 h and peaked at 8–15 h in the urine as well as in the plasma. These results may be useful for designing the dose and dose frequency in intervention studies with tea and for development of biomarkers of tea consumption.
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