Division of Cardiology, Internal Medicine Department, Beijing Hospital, Beijing, P.R. China.
Beijing Institute of Geriatrics, Beijing Hospital, Beijing, P.R. China.
Pharm Biol. 2020 Dec;58(1):630-635. doi: 10.1080/13880209.2020.1785510.
Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug-drug interaction between them is still unknown.
To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both and .
A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug-drug interaction between these two drugs .
The (221.34 ± 53.33 691.18 ± 238.31 ng/mL) and the AUC (1060.97 ± 291.21 3483.03 ± 753.83 μg·h/L) of rivaroxaban increased significantly ( < 0.05) with ticagrelor pre-treatment. The MRT of rivaroxaban increased from 4.41 ± 0.79 to 5.97 ± 1.11 h, while the intrinsic clearance decreased from 9.93 ± 2.55 to 2.89 ± 0.63 L/h/kg (both < 0.05) after pre-treated with ticagrelor. Enzyme kinetic study indicated that ticagrelor decreased rivaroxaban metabolic clearance with the IC value of 14.04 μmol/L.
Our and results demonstrated that there is a drug-drug interaction between ticagrelor and rivaroxaban in rats. Further studies need to be carried out to verify whether similar interactions truly apply in humans and whether these interactions have clinical significance.
利伐沙班和替格瑞洛是治疗心房颤动和急性冠状动脉综合征的两种常用药物。然而，它们之间的药物相互作用仍不清楚。
研究替格瑞洛对大鼠体内利伐沙班药代动力学的影响。
建立了一种灵敏、可靠的 UPLC-MS/MS 法测定大鼠血浆中利伐沙班的浓度。将 10 只 Sprague-Dawley 大鼠随机分为替格瑞洛预处理组（10mg/kg/天，预处理 14 天）和对照组。采用建立的 UPLC-MS/MS 法研究了口服给予利伐沙班（10mg/kg，单次剂量）与替格瑞洛预处理与否的药代动力学。此外，还使用 Sprague-Dawley 大鼠肝微粒体研究了这两种药物之间的药物相互作用。
替格瑞洛预处理组大鼠利伐沙班的 Cmax（221.34±53.33ng/ml与 691.18±238.31ng/ml）和 AUC（1060.97±291.21μg·h/L 与 3483.03±753.83μg·h/L）显著增加（ < 0.05）。利伐沙班的 MRT 从 4.41±0.79 小时增加到 5.97±1.11 小时，而内在清除率从 9.93±2.55 L/h/kg 降低到 2.89±0.63 L/h/kg（均 < 0.05），替格瑞洛预处理后。酶动力学研究表明，替格瑞洛降低了利伐沙班的代谢清除率，IC 值为 14.04μmol/L。
本研究的体内和体外结果表明，替格瑞洛和利伐沙班在大鼠体内存在药物相互作用。需要进一步的研究来验证这些相互作用是否在人体中真实存在，以及这些相互作用是否具有临床意义。
