Pharmacokinetic interaction between dronedarone and ticagrelor following oral administration in rats.

Dronedarone and ticagrelor have high co-administration potential in patients with both acute coronary syndrome and atrial fibrillation. The objective of the present study was to investigate the potential interaction between dronedarone (5 and 10 mg/kg) and ticagrelor (5 and 10 mg/kg) when administered orally to rats. Forty Sprague-Dawley rats were randomly distributed into eight groups; consisting of a dronedarone only group, a ticagrelor only group, a dronedarone with ticagrelor-pretreatment group, and a ticagrelor with dronedarone-pretreatment group. Pharmacokinetic exposure (AUC = 1472 ng·h/mL) associated with administration of 10 mg/kg of dronedarone increased significantly, with delayed in the group that received ticagrelor-pretreatment when compared to the dronedarone only group (AUC = 723 ng·h/mL). In addition, pharmacokinetic exposure (AUC = 2391 ng·h/mL) associated with administration of 10 mg/kg of ticagrelor increased significantly, with increased (0.31 h) and decreased / (14.6 L/kg) in the dronedarone-pretreatment group when compared to the ticagrelor only group (AUC = 1616 ng·h/mL;  = 0.21 h; /  =  31.3 L/kg). Results of our study suggest that further investigation of a potential interaction between dronedarone and ticagrelor in humans is justified and that caution may need to be exercised when dronedarone and ticagrelor pharmacotherapies concomitantly.