This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chow, H-H. S. Articles by Hara, Y. Search for Related Content PubMed PubMed Citation Articles by Chow, H-H. S. Articles by Hara, Y.

Phase I Pharmacokinetic Study of Tea Polyphenols following Single-dose Administration of Epigallocatechin Gallate and Polyphenon E¹

Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85724 [H-H. S. C., Y. C., D. S. A., I. H., R. D., F. S.]; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892 [J. A. C.]; College of Pharmacy, Rutgers University, Piscataway, New Jersey 08854 [C. S. Y.]; and Mitsui Norin Co., Ltd., Shizuoka 426-01, Japan [Y. H.]

Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using high-performance liquid chromatography with the coulometric electrode array detection 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·µg/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively. EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration. There were no significant 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 higher than those after the 200- and 400-mg dose. The AUC and C_max of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols.

This article has been cited by other articles:

				M. W. Anderson, C. Goodin, Y. Zhang, S. Kim, R. D. Estensen, T. S. Wiedmann, P. Sekar, C. R. Buncher, J. C. Khoury, J. R. Garbow, et al. Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in A/J strain mice Carcinogenesis, August 1, 2008; 29(8): 1594 - 1600. [Abstract] [Full Text] [PDF]

				S. M. Henning, J. J. Choo, and D. Heber Nongallated Compared with Gallated Flavan-3-ols in Green and Black Tea Are More Bioavailable J. Nutr., August 1, 2008; 138(8): 1529S - 1534S. [Abstract] [Full Text] [PDF]

				C. Auger, W. Mullen, Y. Hara, and A. Crozier Bioavailability of Polyphenon E Flavan-3-ols in Humans with an Ileostomy J. Nutr., August 1, 2008; 138(8): 1535S - 1542S. [Abstract] [Full Text] [PDF]

				S. Sasazuki, M. Inoue, T. Miura, M. Iwasaki, S. Tsugane, and for the Japan Public Health Center-based Prospecti Plasma Tea Polyphenols and Gastric Cancer Risk: A Case-Control Study Nested in a Large Population-Based Prospective Study in Japan Cancer Epidemiol. Biomarkers Prev., February 1, 2008; 17(2): 343 - 351. [Abstract] [Full Text] [PDF]

				D. L. McKay and J. B. Blumberg Roles for Epigallocatechin Gallate in Cardiovascular Disease and Obesity: An Introduction J. Am. Coll. Nutr., August 1, 2007; 26(4): 362S - 365S. [Abstract] [Full Text] [PDF]

				A. M. Hill, A. M. Coates, J. D. Buckley, R. Ross, F. Thielecke, and P. R.C. Howe Can EGCG Reduce Abdominal Fat in Obese Subjects? J. Am. Coll. Nutr., August 1, 2007; 26(4): 396S - 402S. [Abstract] [Full Text] [PDF]

				D. J. Boocock, G. E.S. Faust, K. R. Patel, A. M. Schinas, V. A. Brown, M. P. Ducharme, T. D. Booth, J. A. Crowell, M. Perloff, A. J. Gescher, et al. Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1246 - 1252. [Abstract] [Full Text] [PDF]

				W. Liang, C. W. Binns, L. Jian, and A. H. Lee Does the Consumption of Green Tea Reduce the Risk of Lung Cancer Among Smokers? Evid. Based Complement. Altern. Med., March 1, 2007; 4(1): 17 - 22. [Abstract] [Full Text] [PDF]

				G. Lu, J. Liao, G. Yang, K. R. Reuhl, X. Hao, and C. S. Yang Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine Cancer Res., December 1, 2006; 66(23): 11494 - 11501. [Abstract] [Full Text] [PDF]

				S. M. Henning, W. Aronson, Y. Niu, F. Conde, N. H. Lee, N. P. Seeram, R.-P. Lee, J. Lu, D. M. Harris, A. Moro, et al. Tea Polyphenols and Theaflavins Are Present in Prostate Tissue of Humans and Mice after Green and Black Tea Consumption J. Nutr., July 1, 2006; 136(7): 1839 - 1843. [Abstract] [Full Text] [PDF]

				F. Spinella, L. Rosano, V. Di Castro, S. Decandia, A. Albini, M. R. Nicotra, P. G. Natali, and A. Bagnato Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma. Mol. Cancer Ther., June 1, 2006; 5(6): 1483 - 1492. [Abstract] [Full Text] [PDF]

				C. Cabrera, R. Artacho, and R. Gimenez Beneficial effects of green tea--a review. J. Am. Coll. Nutr., April 1, 2006; 25(2): 79 - 99. [Abstract] [Full Text] [PDF]

				C. Stresemann, B. Brueckner, T. Musch, H. Stopper, and F. Lyko Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res., March 1, 2006; 66(5): 2794 - 2800. [Abstract] [Full Text] [PDF]

				O. M. Dorchies, S. Wagner, O. Vuadens, K. Waldhauser, T. M. Buetler, P. Kucera, and U. T. Ruegg Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy Am J Physiol Cell Physiol, February 1, 2006; 290(2): C616 - C625. [Abstract] [Full Text] [PDF]

				J. D. Lambert, M.-J. Lee, L. Diamond, J. Ju, J. Hong, M. Bose, H. L. Newmark, and C. S. Yang DOSE-DEPENDENT LEVELS OF EPIGALLOCATECHIN-3-GALLATE IN HUMAN COLON CANCER CELLS AND MOUSE PLASMA AND TISSUES Drug Metab. Dispos., January 1, 2006; 34(1): 8 - 11. [Abstract] [Full Text] [PDF]

				H-H. S. Chow, I. A. Hakim, D. R. Vining, J. A. Crowell, J. Ranger-Moore, W. M. Chew, C. A. Celaya, S. R. Rodney, Y. Hara, and D. S. Alberts Effects of Dosing Condition on the Oral Bioavailability of Green Tea Catechins after Single-Dose Administration of Polyphenon E in Healthy Individuals Clin. Cancer Res., June 15, 2005; 11(12): 4627 - 4633. [Abstract] [Full Text] [PDF]

				M. Shimizu, A. Deguchi, J. T.E. Lim, H. Moriwaki, L. Kopelovich, and I. B. Weinstein (-)-Epigallocatechin Gallate and Polyphenon E Inhibit Growth and Activation of the Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor-2 Signaling Pathways in Human Colon Cancer Cells Clin. Cancer Res., April 1, 2005; 11(7): 2735 - 2746. [Abstract] [Full Text] [PDF]

				C. Manach, G. Williamson, C. Morand, A. Scalbert, and C. Remesy Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies Am. J. Clinical Nutrition, January 1, 2005; 81(1): 230S - 242S. [Abstract] [Full Text] [PDF]

				B. Halliwell, J. Rafter, and A. Jenner Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am. J. Clinical Nutrition, January 1, 2005; 81(1): 268S - 276S. [Abstract] [Full Text] [PDF]

				O. Aktas, T. Prozorovski, A. Smorodchenko, N. E. Savaskan, R. Lauster, P.-M. Kloetzel, C. Infante-Duarte, S. Brocke, and F. Zipp Green Tea Epigallocatechin-3-Gallate Mediates T Cellular NF-{kappa}B Inhibition and Exerts Neuroprotection in Autoimmune Encephalomyelitis J. Immunol., November 1, 2004; 173(9): 5794 - 5800. [Abstract] [Full Text] [PDF]

				M. Nagai, A. H. Conney, and B. T. Zhu STRONG INHIBITORY EFFECTS OF COMMON TEA CATECHINS AND BIOFLAVONOIDS ON THE O-METHYLATION OF CATECHOL ESTROGENS CATALYZED BY HUMAN LIVER CYTOSOLIC CATECHOL-O-METHYLTRANSFERASE Drug Metab. Dispos., May 1, 2004; 32(5): 497 - 504. [Abstract] [Full Text] [PDF]

				D. S. Wheeler, J. D. Catravas, K. Odoms, A. Denenberg, V. Malhotra, and H. R. Wong Epigallocatechin-3-gallate, a Green Tea-Derived Polyphenol, Inhibits IL-1{beta}-Dependent Proinflammatory Signal Transduction in Cultured Respiratory Epithelial Cells J. Nutr., May 1, 2004; 134(5): 1039 - 1044. [Abstract] [Full Text] [PDF]

				J. D. Lambert, M.-J. Lee, H. Lu, X. Meng, J. J. J. Hong, D. N. Seril, M. G. Sturgill, and C. S. Yang Epigallocatechin-3-Gallate Is Absorbed but Extensively Glucuronidated Following Oral Administration to Mice,2 J. Nutr., December 1, 2003; 133(12): 4172 - 4177. [Abstract] [Full Text] [PDF]

				J. B. Vaidyanathan and T. Walle Cellular Uptake and Efflux of the Tea Flavonoid (-)Epicatechin-3-gallate in the Human Intestinal Cell Line Caco-2 J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 745 - 752. [Abstract] [Full Text] [PDF]

				J. D. Lambert and C. S. Yang Mechanisms of Cancer Prevention by Tea Constituents J. Nutr., October 1, 2003; 133(10): 3262S - 3267. [Abstract] [Full Text] [PDF]

				I. A. Hakim, R. B. Harris, S. Brown, H-H. S. Chow, S. Wiseman, S. Agarwal, and W. Talbot Effect of Increased Tea Consumption on Oxidative DNA Damage among Smokers: A Randomized Controlled Study J. Nutr., October 1, 2003; 133(10): 3303S - 3309. [Abstract] [Full Text] [PDF]

				H-H. S. Chow, Y. Cai, I. A. Hakim, J. A. Crowell, F. Shahi, C. A. Brooks, R. T. Dorr, Y. Hara, and D. S. Alberts Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals Clin. Cancer Res., August 1, 2003; 9(9): 3312 - 3319. [Abstract] [Full Text] [PDF]

				M. Masuda, M. Suzui, J. T. E. Lim, and I. B. Weinstein Epigallocatechin-3-gallate Inhibits Activation of HER-2/neu and Downstream Signaling Pathways in Human Head and Neck and Breast Carcinoma Cells Clin. Cancer Res., August 1, 2003; 9(9): 3486 - 3491. [Abstract] [Full Text] [PDF]

				H. Lu, X. Meng, C. Li, S. Sang, C. Patten, S. Sheng, J. Hong, N. Bai, B. Winnik, C.-T. Ho, et al. Glucuronides of Tea Catechins: Enzymology of Biosynthesis and Biological Activities Drug Metab. Dispos., April 1, 2003; 31(4): 452 - 461. [Abstract] [Full Text] [PDF]

				Y. Cai, N. D. Anavy, and H-H. S. Chow Contribution of Presystemic Hepatic Extraction to the Low Oral Bioavailability of Green Tea Catechins in Rats Drug Metab. Dispos., November 1, 2002; 30(11): 1246 - 1249. [Abstract] [Full Text] [PDF]

				M.-J. Lee, P. Maliakal, L. Chen, X. Meng, F. Y. Bondoc, S. Prabhu, G. Lambert, S. Mohr, and C. S. Yang Pharmacokinetics of Tea Catechins after Ingestion of Green Tea and (-)-Epigallocatechin-3-gallate by Humans: Formation of Different Metabolites and Individual Variability Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1025 - 1032. [Abstract] [Full Text] [PDF]

				J. B. Vaidyanathan and T. Walle Glucuronidation and Sulfation of the Tea Flavonoid (-)-Epicatechin by the Human and Rat Enzymes Drug Metab. Dispos., August 1, 2002; 30(8): 897 - 903. [Abstract] [Full Text] [PDF]

				M. Masuda, M. Suzui, and I. B. Weinstein Effects of Epigallocatechin-3-gallate on Growth, Epidermal Growth Factor Receptor Signaling Pathways, Gene Expression, and Chemosensitivity in Human Head and Neck Squamous Cell Carcinoma Cell Lines Clin. Cancer Res., December 1, 2001; 7(12): 4220 - 4229. [Abstract] [Full Text] [PDF]