**5. Conclusions**

After intravenous administration of tofacitinib to G-ARF and C-ARF rats, its AUC was significantly higher than that in control rats due to a significantly lower CLNR (due to a decrease in the protein expressions of the hepatic CYP3A1/2 and CYP2C11 subfamily) and CL<sup>R</sup> (due to a significantly lower CLCR by an impaired kidney function) than in control rats. A reduced dosage of tofacitinib could be considered in patients with renal impairment based on their level of renal dysfunction.

**Author Contributions:** S.H.B. performed all of the animal experiments and the HPLC analysis of tofacitinib in the biological samples and estimated the pharmacokinetic parameters. S.-Y.C. performed the liver and kidney biopsies and interpreted the results. S.H.K. designed the experiments, performed the statistical analysis and graphics work, and drafted the manuscript. All authors have read and approved the final manuscript.

**Funding:** This work was supported by the Korea Health Technology R&D Project (HI16C0992) through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare and the Basic Science Research Program (NRF-2018R1A2B6004895) through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

**Conflicts of Interest:** The authors declare no competing financial interests.
