This project includes two separate pharmacokinetic studies with simvastatin and rosuvastatin,
respectively. Each study is an open-label, single-dose, randomized, three-phase (no herbs,
with green tea, with soy isoflavones) clinical pharmacokinetic study design with a wash-out
of at least 4-weeks between phases. The aim is to examine whether green tea extract and soy
isoflavones affect the pharmacokinetics of simvastatin and rosuvastatin in healthy subjects
and whether these interactions are influenced by polymorphisms in the relevant drug
transporters, solute carrier 1B1 (SLCO1B1) and adenosine triphosphate (ATP) binding cassette
G2 (ABCG2) and to identify whether polymorphisms in drug transporters influence the
pharmacokinetics of simvastatin and rosuvastatin. After informed consent is obtained,
subjects are required to abstain from any prescription or non-prescription medications 2
weeks before and throughout the study. Subjects are given a single dose of simvastatin 20 mg
(Zocor®, MSD) or rosuvastatin 10 mg (Crestor®, Astra Zeneca) on 3 occasions: 1. without
herbs; 2. with green tea extract; 3. with soy isoflavones extract. The green tea extract and
soy isoflavones extract are given at a dose containing epigallocatechin gallate (EGCG) 800 mg
once daily or isoflavones 120 mg once daily for 14 days before statin dosing with at least
4-week washout period between phases. Blood samples are taken at intervals from 0 to 24 hours
on the statin dosing days. During the study, subjects are reminded frequently of the
requirements on diet.