|
|
Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose
Administration of Epigallocatechin Gallate and Polyphenon E in Healthy
Individuals
H-H. Sherry Chow,
Yan Cai, Iman A. Hakim, James A. Crowell,
Farah Shahi, Chris A. Brooks, Robert T. Dorr,
Yukihiko Hara and David S. Alberts
Arizona Cancer Center, The University of Arizona, Tucson,
Arizona 85724 [H-H. S. C.*, Y. C., I. A. H., F. S., C. A. B., R. T. D., D. S.
A.]; College of Pharmacy, The University of Arizona, Tucson, Arizona 85721 [H-H.
S. C., Y. C.]; Division of Cancer Prevention, National Cancer Institute,
Bethesda, Maryland 20892 [J. A. C.]; and Mitsui Norin Co., Ltd., Shizuoka
426-01, Japan [Y. H.]. *To whom requests for reprints should be addressed, at Arizona Cancer
Center, The University of Arizona, Tucson, AZ 85724. Phone: (520)
626-3358; Fax: (520) 626-5348; E-mail: schow@azcc.arizona.edu.
Purpose. Green tea and green tea polyphenols have been shown to
possess cancer preventive activities in preclinical model systems.
In
preparation for future green tea intervention trials, we have
conducted a clinical study to determine the safety and pharmacokinetics
of green tea polyphenols after 4 weeks of daily p.o. administration
of epigallocatechin gallate (EGCG) or Polyphenon E (a defined,
decaffeinated green tea polyphenol mixture).
In an exploratory
fashion, we have also determined the effect of chronic green tea
polyphenol administration on UV-induced erythema response.
Experimental Design. Healthy participants with Fitzpatric skin type
II or III underwent a 2-week run-in period and were randomly assigned
to receive one of the five treatments for 4 weeks: 800 mg EGCG
once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E
once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo
once/day (8 subjects/group).
Samples were collected and measurements
performed before and after the 4-week treatment period for
determination of safety, pharmacokinetics, and biological activity of
green tea polyphenol treatment.
Results. Adverse events reported during the 4-week treatment period
include excess gas, upset stomach, nausea, heartburn, stomach ache,
abdominal pain, dizziness, headache, and muscle pain.
All of the
reported events were rated as mild events.
For most events, the
incidence reported in the polyphenol-treated groups was not more than
that reported in the placebo group.
No significant changes were
observed in blood counts and blood chemistry profiles after repeated
administration of green tea polyphenol products.
There was a >60%
increase in the area under the plasma EGCG concentration-time curve
after 4 weeks of green tea polyphenol treatment at a dosing schedule
of 800 mg once daily.
No significant changes were observed in the
pharmacokinetics of EGCG after repeated green tea polyphenol
treatment at a regimen of 400 mg twice daily.
The pharmacokinetics of
the conjugated metabolites of epigallocatechin and epicatechin were
not affected by repeated green tea polyphenol treatment.
Four weeks
of green tea polyphenol treatment at the selected dose and dosing
schedule did not provide protection against UV-induced erythema.
Conclusions. We conclude that it is safe for healthy individuals to
take green tea polyphenol products in amounts equivalent to the EGCG
content in 8–16 cups of green tea once a day or in divided doses
twice a day for 4 weeks.
There is a >60% increase in the systemic
availability of free EGCG after chronic green tea polyphenol
administration at a high daily bolus dose (800 mg EGCG or Polyphenon
E once daily).
© 2003 American
Association for Cancer Research
|
