1. Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats
- Author
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Da-Peng Dai, Hua-Lan Wu, Hui Jiang, Hao Chen, Quan Zhou, Junpeng Liu, Feifei Chen, Jia Chong, Shuanghu Wang, Jiefu Yang, Yunfang Zhou, Minghui Du, and You Lü
- Subjects
Male ,Acute coronary syndrome ,Ticagrelor ,Drug-drug interaction ,Pharmaceutical Science ,RM1-950 ,Pharmacology ,030226 pharmacology & pharmacy ,01 natural sciences ,Rats, Sprague-Dawley ,03 medical and health sciences ,Rat liver microsomes ,0302 clinical medicine ,Pharmacokinetics ,Rivaroxaban ,Drug Discovery ,Medicine ,Animals ,Drug Interactions ,atrial fibrillation ,drug–drug interaction ,anticoagulation ,business.industry ,rat liver microsomes ,Atrial fibrillation ,General Medicine ,medicine.disease ,0104 chemical sciences ,Rats ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Microsomes, Liver ,Molecular Medicine ,Uplc ms ms ,Therapeutics. Pharmacology ,business ,Platelet Aggregation Inhibitors ,uplc-ms/ms ,medicine.drug ,Factor Xa Inhibitors ,Research Article - Abstract
Context 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. Objective To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. Materials and methods 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 in vitro. Results The Cmax (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC(0–t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 μg·h/L) of rivaroxaban increased significantly (p
- Published
- 2020