## 3 Results
### NVP-13 Is Detectable within the CSF
\begin{table}
\begin{tabular}{c c c c c} \hline \hline  & \begin{tabular}{c} **Dose Level** \\ **(mg/Animal)** \\ \end{tabular} & \begin{tabular}{c} **C\({}_{\text{max}}\)** \\ **(ng/mL)** \\ \end{tabular} & \begin{tabular}{c} **T\({}_{\text{max}}\)** \\ **(h)** \\ \end{tabular} & \
\begin{tabular}{c} **AUC\({}_{\text{0-24}}\)** \\ **(ng-h/mL)** \\ \end{tabular} &
\begin{tabular}{c} **AUC\({}_{\text{0-t}}\)** \\ **(ng-h/mL)** \\ \end{tabular} \\ \hline
2–3 & 0.8 & 181 & 0.500 & 986 & 986 \\
4–5 & 4.0 & 1280 & 0.500 & 6040 & 6040 \\ \hline \hline \end{tabular}  
NA—Not applicable; C\({}_{\text{max}}\) = maximum plasma concentration; T\({}_{\text{max}}\) = time of maximum concentration profile; AUC\({}_{\text{0-24}}\) = area under the plasma concentration-time curve calculated from 0–24 h; AUC\({}_{\text{0-t}}\) = area under the plasma-concentration-time curve calculated from 0–t, where t is the time of the last measurable concentration.  
\end{table} 
Table 8: Summary of Gender-Averaged Toxicokinetic Parameters for NVP13 in Plasma following Single Intrathecal Administration to Cynomolgus Monkeys—Group 2–5. \begin{table}
\begin{tabular}{c c c c c} \hline \hline  & \begin{tabular}{c} **C\({}_{\text{max}}\)** \\ **(ng/mL)** \\ \end{tabular} & \begin{tabular}{c} **T\({}_{\text{max}}\)** \\ **(h)** \\ \end{tabular} & \
\begin{tabular}{c} **AUC\({}_{\text{0-24}}\)** \\ **(ng-h/mL)** \\ \end{tabular} &
\begin{tabular}{c} **AUC\({}_{\text{0-t}}\)** \\ **(ng-h/mL)** \\ \end{tabular} \\ \hline
1 & 63.7 & 1.94 & 396 & 396 \\
8 & 158 & 0.500 & 630 & 630 \\
15 & 42.5 & 7.69 & 308 & 308 \\
22 & 26.6 & 3.38 & 219 & 219 \\
29 & 26.4 & 4.81 & 225 & 225 \\
43 & 93.2 & 7.69 & 184 & 184 \\
57 & 48.0 & 4.81 & 334 & 334 \\
71 & 46.0 & 7.69 & NA & 510 \\
85 & 37.6 & 9.13 & NA & 609 \\ \hline \hline \end{tabular}  
NA—Not applicable; C\({}_{\text{max}}\) = maximum plasma concentration; T\({}_{\text{max}}\) = time of maximum concentration profile; AUC\({}_{\text{0-24}}\) = area under the plasma concentration-time curve calculated from 0–24 h; AUC\({}_{\text{0-t}}\) = area under the plasma-concentration-time curve calculated from 0–t, where t is the time of the last measurable concentration.  
\end{table} 
Table 9: Summary of Gender-Averaged Toxicokinetic Parameters for NVP13 in Plasma following Repeated Intrathecal Administration to Cynomolgus Monkeys at a Nominal Dose Level of 0.4 mg/animal/occasion—Group 6. As already stated above, in order to assess NVP-13 concentrations within CNS regions, AEX-HPLC analysis was performed and NVP-13 was detectable within the main regions of interest, namely the spinal cord (lumbar, thoracic, and cervical), the hippocampus and the subventricular zone (Figure 5A,B) following one single i.th administration, on day 15 and day 29. Figure 5: **Central NVP-13 tissue concentrations (Phase B). ** NVP-13 reaches central nervous system regions of interest following single intrathecal administrations with two different doses, respectively (**A**,**B**). Tissues levels depended on the dose administered. Again, the tissue concentrations decreased with increasing distance from the injection side (lumbar spinal cord). Similar to phase A, NVP-13 concentrations were assessed within CNS regions by AEX-HPLC analysis. NVP-13 was detectable within the CSF and plasma (Figures 6 and 7) following one single i.th administration, on day 15 and day 29. Again, to assess NVP-13 concentrations within peripheral tissue (liver and kidney), AEX-HPLC analysis was performed and, NVP-13 was detectable (Figures 8 and 9), on day 15 and 29. Figure 6: **CSF NVP-13 concentrations (Phase B). ** NVP-13 concentrations are detectable within the CSF in a dose-dependent manner 24 h following one single intrathecal administration (**A–D**).