Interactions of Herbs With Statin Drugs and Potential Mediation by Drug Transporters
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- The interactions of green tea extract and soy isoflavones on the maximum plasma concentration of rosuvastatin
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy Chinese male subjects aged 18 - 45 years
- •healthy volunteers who had been genotyped for the SLCO1B1 388A>G, 521T>C and ABCG2 421C>A polymorphisms.
排除标准
- •Patients with any disease
- •Volunteers who cannot follow the instructions
- •Volunteers who don't sign the informed consent.
研究组 & 干预措施
simvastatin 20 mg (Zocor®, MSD)
simvastatin 20 mg are given on 3 occasions: 1. without herbs; 2. with green tea extract containing EGCG 800 mg once daily for 14 days before statin dosing; 3. with soy isoflavones extract containing isoflavones 120 mg once daily for 14 days before statin dosing, with at least 4-week washout period between phases.
干预措施: Simvastatin 20 mg (Zocor®, MSD) (Drug)
rosuvastatin 10 mg (Crestor®, Astra Zeneca)
rosuvastatin 10 mg are given on 3 occasions: 1. without herbs; 2. with green tea extract containing EGCG 800 mg once daily for 14 days before statin dosing; 3. with soy isoflavones extract containing isoflavones 120 mg once daily for 14 days before statin dosing, with at least 4-week washout period between phases
干预措施: rosuvastatin 10 mg (Crestor®, Astra Zeneca) (Drug)
结局指标
主要结局
The interactions of green tea extract and soy isoflavones on the maximum plasma concentration of rosuvastatin
时间窗: 14 weeks
Maximum plasma concentration for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.
The interactions of green tea extract and soy isoflavones on the area under plasma concentration-time curve of rosuvastatin
时间窗: 14 weeks
Area under plasma concentration-time curve for rosuvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.
The interactions of green tea extract and soy isoflavones on the maximum plasma concentration of simvastatin
时间窗: 14 weeks
Maximum plasma concentration for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.
The interactions of green tea extract and soy isoflavones on the area under plasma concentration-time curve of simvastatin
时间窗: 14 weeks
Area under plasma concentration-time curve for simvastatin comparing: 1. without herbs; 2. with green tea extract; 3. with soy isoflavones extract.
次要结局
- The influence of polymorphisms in drug transporters on the maximum plasma concentration of simvastatin and the interaction with herbs.(14 weeks)
- The influence of polymorphisms in drug transporters on the area under plasma concentration-time curve of simvastatin and the interaction with herbs.(14 weeks)
- The influence of polymorphisms in drug transporters on the maximum plasma concentration of rosuvastatin and the interaction with herbs.(14 weeks)
- The influence of polymorphisms in drug transporters on the area under plasma concentration-time curve of rosuvastatin and the interaction with herbs.(14 weeks)
研究者
Brian Tomlinson
Professor
Chinese University of Hong Kong