In Vivo Interaction Study
|Sample||Compound measured||Value||Measurement||Study sequence||Additional information||N replicates|
Total voided urine was collected for 8 h after probe drug administration.
Eligible subjects underwent a 4-week washout period, in which they were required to refrain from tea or its related products and herbal/botanical supplement, and to minimize the consumption of cruciferous vegetables. Subjects were required to abstain from caffeine-containing products and food items that have been reported to affect drug-metabolizing enzymes (e.g., grapefruit juice, cruciferous vegetables, and food cooked over charcoal), and over-the-counter medications beginning 72 h before and until 8 h after the probe drug administration. Study subjects were instructed to fast overnight for 8 h before and until 4 h after the administration of the probes.
Probe cocktail study
There were 10 male and 32 female participants. Average age was 38 years (range, 19-73 years) and average body mass index was 24 kg/m2 (range, 19- 37 kg/m2). The participants had normal liver and renal function. Participants were excluded if they were pregnantor breast feeding, had invasive cancers within the past 5 years, had uncontrolled severe metabolic disorders or other serious acute or chronic diseases, consumed more than three drinks of alcohol per week on average, consumed tea regularly, had known hypersensitivity to green tea or metabolic probe drugs (caffeine, dextromethorphan, losartan, or buspirone), were taking medications/supplements that are known CYP enzyme inducers or inhibitors, or had participated in other clinical research studies within the past 3 months.
before and at 0.5, 1, 2, 4, 6, and 8 h after dosing
Drug or Natural Product Administration
single dose, as a cocktail, before and after Polyphenon E administration
4 Polyphenon E capsules (800 mg epigallocatechin gallate)
once daily in the morning
Chemoprevention Agent Development Research Group, National Cancer Institute (Bethesda, MD)
Polyphenon E, formulated as p.o. capsules (200 mg of EGCG per capsule)
Polyphenon E is a green tea catechin extract produced by Mitsui Norin, Ltd (Shizuoka, Japan). It contains 80% to 98% total catechins by weight with epigallocatechin gallate as the main component accounting for 50% to 75% of the material. Other catechins, including epicatechin, epigallocatechin, epicatechin gallate, and gallocatechin gallate, are present in levels ranging from ~2% to 12% each. Polyphenon E contains small quantities of caffeine (around 0.5% w/w) and can be considered a decaffeinated product.
Pharmacodynamics (PD) & Adverse Events
All reported adverse events were Common Toxicity Criteria grade 1 or 2, and many were very mild and transient. Nineteen subjects reported at least one episode of nausea that was deemed possibly or probably related to Polyphenon E administration. Nausea was generally very mild (grade 1) and resolved when the morning meal was taken an hour after dosing.