**4. Conclusions**

In our study, the plasma concentration-time profile of tadalafil was significantly changed by co-administration with ticagrelor. A ticagrelor-inhibited CYP3A-mediated tadalafil metabolism and the systemic exposure of tadalafil increased by pretreatment with ticagrelor. Co-administration of tadalafil with ticagrelor increased the AUC of tadalafil by approximately 61% and decreased the clearance of tadalafil by 37%. These results sugges<sup>t</sup> that the co-administration of tadalafil and ticagrelor may need dose control and specific drug therapy to avoid side e ffects from drug-drug interactions. Therefore, CAD patients receiving ticagrelor should be closely monitored when administering tadalafil concomitantly. For further studies, an additional experiment is expected to identify the variation of clinical e fficacy of tadalafil by co-administration with ticagrelor, a CYP3A4 inhibitor.

**Author Contributions:** Conceptualization, Y.-G.N.; methodology, Y.-G.N. and J.-J.B.; software, Y.-G.N. and J.-J.B.; validation, H.-W.H. and J.-J.B.; formal analysis, J.-J.B. and H.-W.H.; investigation, Y.-G.N. and J.-J.B.; resources, M.-K.K.; data curation, Y.-G.N.; writing—original draft preparation, Y.-G.N. and J.-J.B.; writing—review and editing, Y.-G.S., H.-K.L., and C.-W.C.; supervision, C.-W.C.

**Funding:** This work was supported by the Basic Science Research Program (2016R1A2B4011294) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology.

**Acknowledgments:** The materials were kindly supported by Korea United Pharma Inc.

**Conflicts of Interest:** The authors declare no conflict of interest.
