Zeng Weiwei, Hu Miao, Lee Hon Kit, Wat Elaine, Lau Clara Bik San, Ho Chung Shun, Wong Chun Kwok, Tomlinson Brian
Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China.
Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong SAR, China.
Front Nutr. 2022 Mar 24;9:850318. doi: 10.3389/fnut.2022.850318. eCollection 2022.
Green tea and soy products are extensively consumed in daily life. Research has shown that green tea catechins and soy isoflavones may influence the activity of drug metabolizing enzymes and drug transporters. We examined whether regular consumption of green tea extract or soy isoflavones affected the pharmacokinetics of a single dose of rosuvastatin in healthy subjects and whether any interactions were influenced by the polymorphism in the drug transporter ABCG2.
This was an open-label, three-phase randomized crossover study with single doses of rosuvastatin.
Healthy Chinese male subjects were given a single dose of rosuvastatin 10 mg on 3 occasions: 1. without herbs; 2. with green tea extract; 3. with soy isoflavone extract. The green tea and soy isoflavone extract were given at a dose containing EGCG 800 mg once daily or soy isoflavones-80 mg once daily for 14 days before statin dosing and at the same time as the statin dosing with at least 4-weeks washout period between phases.
Twenty healthy male subjects completed the study and the intake of green tea extract significantly reduced the systemic exposure to rosuvastatin by about 20% reducing AUC from [geometric mean (% coefficient of variation)] 108.7 (28.9) h·μg/L to 74.1 (35.3) h·μg/L and C from 13.1 (32.2) μg/L to 7.9 (38.3) μg/L ( < 0.001 for both), without affecting the elimination half-life. The ABCG2 421C>A polymorphism had a significant effect on rosuvastatin exposure but no impact on the interaction with green tea. Soy isoflavones had no significant effect on rosuvastatin pharmacokinetics.
This study showed that repeated administration of green tea extract significantly reduced the systemic exposure of rosuvastatin in healthy volunteers. These effects might be predicted to either reduce or increase the lipid-lowering effect of rosuvastatin depending on the mechanism of the effect.
绿茶和豆制品在日常生活中被广泛食用。研究表明，绿茶儿茶素和大豆异黄酮可能会影响药物代谢酶和药物转运体的活性。我们研究了长期饮用绿茶提取物或大豆异黄酮是否会影响健康受试者单次服用瑞舒伐他汀的药代动力学，以及药物转运体ABCG2的多态性是否会影响任何相互作用。
这是一项开放标签、三阶段的随机交叉研究，受试者单次服用瑞舒伐他汀。
健康中国男性受试者分3次服用单次剂量的10 mg瑞舒伐他汀：1. 不服用草药；2. 服用绿茶提取物；3. 服用大豆异黄酮提取物。在他汀类药物给药前14天，每天给予一次含800 mg表没食子儿茶素没食子酸酯（EGCG）的绿茶提取物剂量或每天一次80 mg大豆异黄酮剂量，并在他汀类药物给药时同时服用，各阶段之间至少有4周的洗脱期。
20名健康男性受试者完成了研究，摄入绿茶提取物使瑞舒伐他汀的全身暴露量显著降低约20%，曲线下面积（AUC）从[几何均值（变异系数%）]108.7（28.9）h·μg/L降至74.1（35.3）h·μg/L，血药浓度（C）从13.1（32.2）μg/L降至7.9（38.3）μg/L（两者均P<0.001），且不影响消除半衰期。ABCG2 421C>A多态性对瑞舒伐他汀的暴露有显著影响，但对与绿茶的相互作用无影响。大豆异黄酮对瑞舒伐他汀的药代动力学无显著影响。
本研究表明，重复给予绿茶提取物可显著降低健康志愿者体内瑞舒伐他汀的全身暴露量。根据其作用机制，这些影响可能会降低或增加瑞舒伐他汀的降脂效果。
