Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China.
Department of Clinical Pharmacology, The Frist Affiliated Hospital of Soochow University, Suzhou, China.
Curr Drug Metab. 2020;21(6):471-478. doi: 10.2174/1389200221666200514133355.
Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin.
This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism.
Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS).
GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050).
GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.
绿茶可以抑制 OATPs，因此它可能与 OATPs 的底物如瑞舒伐他汀发生相互作用。
本研究旨在探讨绿茶对瑞舒伐他汀药代动力学的影响及其机制。
雄性 Sprague-Dawley 大鼠给予不同剂量的绿茶提取物（GTE）和（-）-表没食子儿茶素-3-没食子酸酯（EGCG）。采用 Caco-2 细胞和 OATP1B1-HEK293T 细胞进行药物摄取和转运试验。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定瑞舒伐他汀和儿茶素的基质浓度。
GTE 和 EGCG 均使瑞舒伐他汀的血浆浓度-时间曲线下面积（AUC0-∞）增加（p<0.050）。在 Caco-2 细胞模型中，GTE 组瑞舒伐他汀的摄取和转运分别增加了 1.94 倍（p<0.001）和 2.11 倍（p<0.050），而 EGCG 组则分别降低了 22.62%和 44.19%（p<0.050）。在 OATP1B1-HEK293T 细胞模型中，GTE 将 OATP1B1 介导的瑞舒伐他汀摄取降低至对照的 35.02%（p<0.050），EGCG 将其降低至对照的 45.61%（p<0.050）。
GTE 增加了大鼠体内瑞舒伐他汀的暴露量。其机制可能包括通过抑制 OATP1B1 增加瑞舒伐他汀的吸收和减少肝脏分布。EGCG 可能是影响瑞舒伐他汀药代动力学参数的绿茶主要成分。我们的结果表明进行绿茶-瑞舒伐他汀研究的重要性。
