Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats.

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 and .

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 .

RESULTS

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.

CONCLUSIONS

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.