**4. Conclusions**

This study successfully developed a simple, sensitive, and validated HPLC-FL method for simultaneous determination of REP and CEL in rat plasma. The new bioanalytical method provided several merits, including good sensitivity, high extraction recovery, negligible matrix effect, and simplicity of sample preparation procedures. The application of this method in the study of pharmacokinetic interactions between REP and CEL revealed that the pharmacokinetics of oral CEL were significantly altered by concurrent administration with oral REP. Furthermore, an in vitro metabolism and protein binding study using HLM and human plasma highlighted the possibility of metabolism-based interactions between CEL and REP in clinical settings. Therefore, the bioanalytical method proposed herein could become a promising tool for preclinical pharmacokinetic studies and, by extension, clinical use after partial modification and validation.

**Supplementary Materials:** The following is available online at http://www.mdpi.com/1999-4923/11/8/382/s1, Table S1. pharmacokinetic parameters of intravenous repaglinide (REP) and celecoxib (CEL) reported in previous studies on rats.

**Author Contributions:** Conceptualization, D.-G.H., H.Y., and I.-S.Y.; Formal analysis, D.-G.H., J.K., S.-W.S., J.-M.K., and I.-S.Y.; Funding acquisition, H.Y. and I.-S.Y.; Investigation, D.-G.H., J.K., S.-W.S., J.-M.K., H.Y., and I.-S.Y.; Methodology, D.-G.H., J.K., J.-W.Y., Y.J., Y.-H.L., M.-S.K., Y.-S.J., H.Y., and I.-S.Y.; Software, H.Y. and I.-S.Y.; Supervision, I.-S.Y.; Validation, D.-G.H.; Writing—original draft, D.-G.H., J.K., H.Y., and I.-S.Y.; Writing—review & editing, J.-W.Y., Y.J., Y.-H.L., M.-S.K., Y.-S.J., H.Y., and I.-S.Y.

**Funding:** This research was supported by PNU-RENovation (2018–2019) and by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Education (NRF-2017R1D1A3B03030252) and by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9G7072568).

**Conflicts of Interest:** The authors have declared no conflict of interest.
