**5. Conclusions**

After intravenous and oral administration of both drugs, the significantly greater AUC of metformin could be due to the inhibition of OCT2-mediated renal excretion of metformin by verapamil, leading to increased systemic exposure of metformin. Interestingly, there was no interaction effect on the metformin concentration in the liver in spite of the inhibitory effect of verapamil on OCT1-mediated metformin uptake in vitro. In contrast, metformin did not influence the pharmacokinetic profile of verapamil. These results can provide essential knowledge about the drug interaction potential between metformin and verapamil for their clinical applications.

**Author Contributions:** Conceptualization, methodology and writing—original draft preparation, S.Y.H. and Y.H.C.; investigation, S.Y.H.; writing—review and editing, S.Y.H. and Y.H.C.; resources and supervision, Y.H.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2016R1C1B2010849 and NRF-2018R1A5A2023127).

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