## 6 Activity Against TB and Combination Study of Delpazolid with Other Anti-TB Agents  
Studies of the early development of delpazolid focused on Gram-positive bacteria. The efficacy of delpazolid on Gram-positive bacteria was similar or slightly better than that of linezolid. For example, in animal studies of systemic infection [17], soft tissue infection, lung infection, and thigh infection models in mice, delpazolid showed greater efficacy than linezolid (data not shown). To evaluate the efficacy of delpazolid in TB, an in vitro susceptibility test was conducted for _M. tuberculosis_ H37 Rv. Compared to linezolid, the minimum inhibitory concentration (MIC) for _M. tuberculosis_ H37 Rv was similar to that under delpazolid; however, the minimum bactericidal concentration was more than 4-fold lower under delpazolid (Table 5). The MIC\({}_{90}\) values of delpazolid for MDR/extensively drug resistant (XDR) TB isolates were 0.25 and 1 \(\mu\)g/mL, respectively. However, an in vitro study of MDR/XDR TB isolates from China showed that the resistance rate varied considerably. The resistance of MDR-TB to linezolid was 6.7%, whereas that \begin{table}
\begin{tabular}{l l l l} \hline
**Pharmacokinetic** & **IV Infusion;** & **IV Infusion;** & **PO;** \\
**Parameter 1 ** & **200 mg (n=6)** & **400 mg (n=8)** & **800 mg (n=8)** \\ \hline C\({}_{\text{max}}\) (\(\mu\)g/mL) & 2.92 \(\pm\) 0.46 & 5.25 \(\pm\) 0.96 & 8.20 \(\pm\) 3.47 \\ T\({}_{\text{max}}\) (hr) & 0.83 \(\pm\) 0.13 & 0.84 \(\pm\) 0.13 & 1.22 \(\pm\) 0.98 \\ T\({}_{\text{1/2}}\) (hr) & 1.70 \(\pm\) 0.26 & 1.48 \(\pm\) 0.16 & 1.64 \(\pm\) 0.48 \\ AUC\({}_{\text{0-24h}}\) (\(\mu\)g:hr/mL) & 5.59 \(\pm\) 0.98 & 9.39 \(\pm\) 1.46 & 18.65 \(\pm\) 4.88 \\ AUC\({}_{\text{inf}}\) (\(\mu\)g:hr/mL) & 5.63 \(\pm\) 1.00 & 9.42 \(\pm\) 1.47 & 18.86 \(\pm\) 4.99 \\ V\({}_{\text{ss}}\), V\({}_{\text{2}}\)/F (L/kg) & 0.90 \(\pm\) 0.06 & 1.05 \(\pm\) 0.20 & 1.67 \(\pm\) 0.79 \\ CL, C/F (L/hr/kg) & 0.56 \(\pm\) 0.10 & 0.67 \(\pm\) 0.10 & 0.69 \(\pm\) 0.18 \\ MRT\({}_{\text{last}}\) (hr) & 1.55 \(\pm\) 0.21 & 1.53 \(\pm\) 0.14 & 2.87 \(\pm\) 0.92 \\ C\({}_{\text{max}}\) norm (\(\mu\)g/mL) & 0.95 \(\pm\) 0.15 & 0.85 \(\pm\) 0.16 & 0.67 \(\pm\) 0.28 \\ AUC\({}_{\text{inf}}\), norm (\(\mu\)g:hr/mL) & 1.83 \(\pm\) 0.33 & 1.53 \(\pm\) 0.24 & 1.53 \(\pm\) 0.40 \\ F (\%) & - & - & 99.8 \(\pm\) 20.6 \\ \hline \end{tabular}
\end{table} 
Table 4: Phase 1 study: summary of delpazolid pharmacokinetic parameters. IV infusion 400 mg and PO 800 mg, cross-over study IV administration of delpazolid was generally safe and well-tolerated 800 mg (PO): Bioavailability was approximately 99% switchable between the PO and IV, with no dose adjustment. \begin{table}
\begin{tabular}{l l l} \hline
**Drug Activities / Resistant Rate 1 ** \\ \hline \end{tabular}
\end{table} 
Table 5: Drug activities and resistance rates of linezolid and delpazolid. to delpazolid was 0.8%, suggesting higher potential efficacy of delpazolid in the treatment of MDR-TB, although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates [18]. Therefore, delpazolid has been considered as a targeted application for MDR-TB treatment. Considering the significantly lower resistance rate of MDR-TB against delpazolid despite its similar structure to linezolid, further studies are needed to investigate structural variations in delpazolid to evaluate the correlations between the structures of various delpazolid derivatives and their resistance rates. In addition, intracellular MICs of delpazolid that can inhibit the growth of intracellular _M. tuberculosis_ H37 Rv revealed efficacy levels similar to those of linezolid under low concentrations, whereas delpazolid had greater efficacy at higher concentrations (Figure 3). The treatment of tuberculosis requires a combination of several antimicrobial agents and long-term therapy [19]. Therefore, evaluating synergy with other anti-TB agents is a crucial step in finding drugs that can be co-administered with delpazolid.