Pharmacokinetics and safety of green tea @entity6398 after multiple-dose administration of XXXX and polyphenon E in healthy individuals.

@entity3978 @entity1 @entity1296 @entity15359 @entity390 @entity5 @entity12919 @entity3089 @entity3090 @entity5105 @entity10 @entity158 @entity272 @entity490 @entity6398 @entity925
PURPOSE: Green tea and green tea @entity6398 have been shown to possess @entity5 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 @entity6398 after 4 weeks of daily p.o. administration of @entity3089 ( @entity3090 ) or Polyphenon E (a defined, decaffeinated green tea @entity3978 mixture). In an exploratory fashion, we have also determined the effect of chronic green tea @entity3978 administration on UV-induced @entity5105 response. EXPERIMENTAL DESIGN: Healthy @entity1 with @entity272 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 @entity3090 once/day, 400 mg @entity3090 twice/day, 800 mg @entity3090 as Polyphenon E once/day, 400 mg @entity3090 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 @entity3978 treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, @entity390 , heartburn, @entity158 , @entity490 , @entity1296 , @entity10 , and @entity925 . All of the reported events were rated as mild events. For most events, the incidence reported in the @entity3978 -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 @entity3978 products. There was a >60% increase in the area under the plasma @entity3090 concentration-time curve after 4 weeks of green tea @entity3978 treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of @entity3090 after repeated green tea @entity3978 treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of @entity15359 and @entity12919 were not affected by repeated green tea @entity3978 treatment. Four weeks of green tea @entity3978 treatment at the selected dose and dosing schedule did not provide protection against UV-induced @entity5105 . CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea @entity3978 products in amounts equivalent to the @entity3090 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 @entity3090 after chronic green tea @entity3978 administration at a high daily bolus dose (800 mg @entity3090 or Polyphenon E once daily).
