**5. Conclusions**

The pharmacokinetic parameters of LOX and its active metabolite were significantly altered when LOX was co-administered with CYP3A activity modulators. In clinical practice, LOX is administered concurrently with many other drugs. Therefore, more studies are needed to assess the possible interactions of LOX with CYP enzymes. In this study, pharmacodynamic interactions were not evaluated; however, they will be evaluated in future studies.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/11/9/479/s1, Figure S1: Representative chromatograms: (A) blank plasma (B), standard loxoprofen (LOX), and its metabolites in plasma. LOX and its metabolites in plasma after administering 20 mg/mL LOX to the (C) VH (Corn oil) group (*n* = *3*), (D) DEX-treated group (*n* = *3*), (E) VH (10% Ethanol) group (*n* = 3), and (F) KTC-treated group (*n* = *3*), Figure S2: CYP induction by dexamethasone (*n* = *3*) (A), and CYP inhibition by ketoconazole (*n* = *3*) (B), Figure S3: Representative EICs of Loxoprofen (LOX) and its metabolites in mouse plasma: VH (Corn oil) group (*n* = *3*) (A), DEX-treated group (*n* = *3*) (B), VH (10% Ethanol) group (*n* = *3*) (C), and KTC-treated group (*n* = *3*) (D), Figure S4: Representative EICs of loxoprofen (LOX) and its metabolites in mouse blank plasma (A) as well as standard LOX and tolbutamide (IS) (B), Figure S5: MS/MS spectra of Loxoprofen (A), M1 (B), M2 (C), M3 (D), M4 (E), M5 (F), M6 (G), and M7 (H), Table S1: Method validation table (*n* = *3*), Table S2: Characterization of loxoprofen (LOX) metabolites identified in mouse plasma along with their average % of area (*n* = 3).

**Author Contributions:** Conceptualization, S.L.; Data Curation, S.P. and S.L.; Formal Analysis, S.P.; P.C.; R.S. and Y.K., Funding Acquisition, T.L. and S.L.; Methodology, S.P.; Resources, A.S., T.C.J., and E.-S.L., Writing – Original Draft Preparation, S.P.; Writing – Review & Editing, J.-H.K. and S.L.

**Funding:** This research was supported by a gran<sup>t</sup> from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1501), and the Korea Basic Science Institute (KBSI) National Research Facilities & Equipment Center (NFEC) gran<sup>t</sup> funded by the Korea Government (Ministry of Education) (No.2019R1A6C1010001).

**Conflicts of Interest:** The authors report no conflicts of interest.
