The Interaction of Herbs and Statins
Condition: Drug Interaction
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      Healthy Chinese male subjects aged 18-45 years are recruited from a pool of over 200 healthy
      volunteers who had been genotyped for the SLCO1B1 388A>G, 521T>C and ABCG2 421C>A
      polymorphisms. All subjects are required to abstain from any prescription or non-prescription
      medications 2 weeks before and throughout the study. They are not allowed to take alcohol,
      tea, grapefruit juice, caffeine, soybean milk or dietary supplements and herbal products 2
      weeks before and throughout the entire study period. They are also not allowed to smoke 2
      weeks before and throughout the study. Subjects are requested to fast for 10 h before and 4 h
      after drug administration during the blood sampling sessions. Meals are standardized and
      consumed at 4 h and 10 h post dosing. Drinking water are not allowed from 1 h pre-dose to 1 h
      post-dose except that needed for drug dosing at the time of blood sampling sessions. 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 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.
    

Intervention name(s): Simvastatin 20 mg (Zocor®, MSD); rosuvastatin 10 mg (Crestor®, Astra Zeneca)
Intervention type(s): Drug; Drug
Intervention description(s): Simvastatin 20 mg given once alone, once with green tea extract and once with soy isoflavones extract.; rosuvastatin 10 mg are given once alone, once with green tea extract and once with soy isoflavones extract.
Other intervention name(s): Green tea extract; Soy isoflavones extract; Green tea extract; Soy isoflavones extract
Intervention MeSH terms: Rosuvastatin Calcium; Simvastatin
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Open-label, single-dose, randomized, three-phase (no herbs, with green tea, with soy isoflavones), once with rosuvastatin and once with simvastatin.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Statins