Effect of aspirin, potential P-glycoprotein activator on intestinal absorption of ticagrelor

Abstract

Background: Ticagrelor is a new P2Y12 receptor inhibitor, which is approved for use in patients with acute coronary syndrome in combination with aspirin. However, there is some evidence that high-dose aspirin reduces the effectiveness of ticagrelor. Given the fact that aspirin can enhance intestinal P-glycoprotein (P-gp) expression and ticagrelor is a substrate of P-gp, we hypothesized that concurrent treatment with aspirin may decrease the intestinal absorption of ticagrelor. Methods and Results: In vitro assay using a monolayer of human epithelial colorectal (Caco-2) cells and in vivo study using the closed-loop method in rats were performed. Aspirin was administered to Caco-2 cells (0.5 and 1 mmol/l) in vitro for 72 hours and to rat intestine (10 mg/kg and 100 mg/kg) in vivo for 4 weeks, before administration of ticagrelor. Ticagrelor permeabilization in vitro was not affected by aspirin pre-treatment and was neither influenced by the P-gp inhibitor, tariquidar. Furthermore, different doses of aspirin (10 mg/kg and 100 mg/kg) pre-treatment did not affect the absorption of ticagrelor in the rat intestine. Conclusion: The intestinal absorption of ticagrelor was not affected by enhancement of P-glycoprotein following prolonged aspirin treatment. Further studies will be necessary to clarify how aspirin attenuates the treatment effect of ticagrelor.