## 4 Discussion
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Dose** & **Tissue** & **T\({}_{\text{max}}\) (h)** & **T\({}_{\text{1/2}}\) (h)** &
\begin{tabular}{c} **AUC\({}_{\text{co}}\)/Dose** \\ **(h\(\cdot\)g/g Tissue/Dose)** \\ \end{tabular} & **AUC Ratio** \\ \hline \multirow{7}{*}{1 mg/kg} & plasma & 1.917 \(\pm\) 1.20 & 3.462 \(\pm\) 0.24 & 1.340 \(\pm\) 0.26 & 1.000 \(\pm\) 0.00 \\  & stomach & 1.250 \(\pm\) 1.37 & 4.557 \(\pm\) 0.77 & 14.60 \(\pm\) 6.60 & 11.94 \(\pm\) 7.25 \\  & small intestine & 1.167 \(\pm\) 1.40 & 3.055 \(\pm\) 0.76 & 11.74 \(\pm\) 3.77 & 8.961 \(\pm\) 2.95 \\  & large intestine & 5.000 \(\pm\) 2.45 & 5.559 \(\pm\) 1.57 & 12.11 \(\pm\) 3.41 & 9.461 \(\pm\) 3.92 \\  & kidney & 3.000 \(\pm\) 1.10 & 20.78 \(\pm\) 0.65 & 92.88 \(\pm\) 7.02 & 71.56 \(\pm\) 14.2 \\  & liver & 0.833 \(\pm\) 0.61 & 6.627 \(\pm\) 1.30 & 8.077 \(\pm\) 1.14 & 6.089 \(\pm\) 0.45 \\  & heart & 2.167 \(\pm\) 0.98 & 4.804 \(\pm\) 1.61 & 2.213 \(\pm\) 0.34 & 1.672 \(\pm\) 0.34 \\  & lung & 1.667 \(\pm\) 1.33 & 7.090 \(\pm\) 1.49 & 2.580 \(\pm\) 0.28 & 1.954 \(\pm\) 0.19 \\  & spleen & 2.250 \(\pm\) 1.47 & 3.608 \(\pm\) 0.39 & 0.353 \(\pm\) 0.11 & 0.259 \(\pm\) 0.04 \\  & testis & 5.667 \(\pm\) 2.66 & 11.26 \(\pm\) 1.11 & 0.767 \(\pm\) 0.17 & 0.575 \(\pm\) 0.09 \\ \hline \multirow{7}{*}{3 mg/kg} & plasma & 0.917 \(\pm\) 0.20 & 4.186 \(\pm\) 1.37 & 1.386\(\pm\)0.43 & 1.000 \(\pm\) 0.00 \\  & stomach & 0.917 \(\pm\) 0.58 & 5.366 \(\pm\) 0.70 & 15.76 \(\pm\) 4.97 & 12.63 \(\pm\) 6.50 \\  & small intestine & 0.833 \(\pm\) 0.26 & 2.974 \(\pm\) 0.63 & 12.425 \(\pm\) 2.92 & 9.970 \(\pm\) 4.64 \\  & large intestine & 6.333 \(\pm\) 2.66 & 4.866 \(\pm\) 0.64 & 18.69 \(\pm\) 8.61 & 14.79 \(\pm\) 8.11 \\  & kidney & 1.167 \(\pm\) 0.41 \({}^{**}\) & 17.59 \(\pm\) 0.48 \({}^{***}\) & 35.49 \(\pm\) 1.22 \({}^{***}\) & 28.64 \(\pm\) 11.9 \({}^{***}\) \\  & liver & 0.917 \(\pm\) 0.20 \({}^{*}\) & 5.771 \(\pm\) 0.53 & 8.033 \(\pm\) 1.30 & 6.214 \(\pm\) 1.79 \\  & heart & 0.917 \(\pm\) 0.20 \({}^{*}\) & 5.370 \(\pm\) 5.06 & 2.407 \(\pm\) 0.95 & 1.730 \(\pm\) 0.33 \\  & lung & 0.917 \(\pm\) 0.20 & 6.266 \(\pm\) 0.31 & 2.354 \(\pm\) 0.20 & 1.849 \(\pm\) 0.60 \\  & spleen & 0.917 \(\pm\) 0.20 & 3.720 \(\pm\) 0.85 & 0.583 \(\pm\) 0.33 & 0.431 \(\pm\) 0.19 \\  & testis & 8.000 \(\pm\) 0.00 & 11.19 \(\pm\) 2.00 & 0.862 \(\pm\) 0.13 & 0.704 \(\pm\) 0.35 \\ \hline \hline \end{tabular} Data are expressed as mean \(\pm\) SD (\(n=6\)). \({}^{*}\)_p_ \(<\) 0.05, \({}^{**}\)_p_ \(<\) 0.01, \({}^{***}\)_p_ \(<\) 0.001 compared with the 1 mg/kg dose group by Mann–Whitney U test.  
\end{table} 
Table 7: Pharmacokine parameters of enavogliflozin in mice following single oral administration of enavogliflozin at doses of 1 and 3 mg/kg. between fasted and fed states and between single and repeated administrations, providing useful information for the evaluation of the new therapeutic efficacy of enavogliflozin. Plasma concentrations of enavogliflozin did not change regardless of whether it was administered to fed or fasted mice. Additionally, plasma concentrations were not altered by repeated oral administration of enavogliflozin for one or 2 weeks (Figures 3 and 4). The pharmacokinetic differences between single and repeated doses of enavogliflozin within 2 weeks are acceptable, indicating that enavogliflozin does not accumulate in the body after repeated dosing within this time frame in mice. Taken together, these results suggest that plasma concentrations of enavogliflozin can be consistently maintained during repeated drug treatment, and thus the oral BA of enavogliflozin may not be changed under prandial and fasting conditions or under repeated dosing conditions, which provide the information for the dose regimen to evaluate its therapeutic potential in mice. We performed these experiments in male mice because we focused on the pharmacokinetic properties of enavogliflozin in fed and fasted conditions, as well as the pharmacokinetic differences between single and repeated doses.