## 3 Results
### NVP-13 Is Detectable within the CSF  
To assess NVP-13 concentrations within CSF, AEX-HPLC analysis was performed in all three phases of the present study. In all phases, NVP-13 was detectable within the CSF (Figure 3B, Figures 7 and 12). A summary of gender-averaged toxicokinetic parameters for NVP-13 in CSF is given in Tables 3-6. NVP-13 exerts dose-dependent effects on CSF toxicokinetic parameters in Phase A (Table 3), Phase B (Table 4), and Phase C (Tables 5 and 6). Figure 4: Peripheral NVP-13 tissue concentrations (Phase A). NVP-13 is slightly detectable within plasma samples up to 24 h, with a maximum concentration 0.5 h following intrathecal administration (**A**). Within liver and kidney samples, NVP-13 is also measurable following repeated intrathecal administrations with escalating doses (**B,C**). \begin{table}
\begin{tabular}{c c c c c} \hline \hline  & \(\mathbf{C_{max}}\) & \(\mathbf{T_{max}}\) & \(\mathbf{AUC_{0-24}}\) & \(\mathbf{AUC_{0-4}}\) \\
**Day** & **(ng/mL)** & **(h)** & **(ng/h/mL)** & **(ng/h/mL)** \\ \hline
1 & 9830 & 42.0 & NA & NA \\
8 & 314 & 60.0 & NA & 22,800 \\
15 & 13,600 & 21.0 & NA & 511,000 \\
22 & 35,700 & 24.0 & NA & 1,210,000 \\
29 & 12,100 & 24.0 & NA & 796,000 \\
43 & 26,500 & 24.0 & NA & 1,560,000 \\
57 & 30,700 & 63.0 & NA & 2,060,000 \\
71 & 22,700 & 24.0 & NA & 1,370,000 \\
85 & 30,400 & 24.0 & NA & 1,040,000 \\ \hline \hline \end{tabular}  
NA—Not applicable. \(\mathbf{C_{max}}\) = maximum CSF concentration; \(\mathbf{T_{max}}\) = time of maximum concentration profile; \(\mathbf{AUC_{0-24}}\) = area under the CSF concentration-time curve calculated from 0–24 h; \(\mathbf{AUC_{0+}}\) = area under the CSF-concentration-time curve calculated from 0–4, where t is the time of the last measurable concentration.  
\end{table} 
Table 6: Summary of Gender-Averaged Toxicokinetic Parameters for NVP13 in CSF following Repeated Intrathecal Administration to Cynomolgus Monkeys at a Nominal Dose Level of 4 mg/animal/occasion—Group 7. \begin{table}
\begin{tabular}{c 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
8 & 0.4 & 58.6 & 6.25 & 343 & 343 \\
15 & 0.8 & 41.7 & 12.0 & 788 & 788 \\
22 & 4.0 & 663 & 6.25 & 5230 & 3900 \\
29 & 20.0 & 1250 & 0.500 & 10,400 & 10,400 \\ \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 7: Summary of Gender-Averaged Toxicokinetic Parameters for NVP13 in Plasma following Intrathecal Administration to Cynomolgus Monkeys at Escalating Dose Levels—Group 1.