Table 2.
NMR plasma and CSF PK exposures estimated using Bayesian posteriors for AUC0-endoftreatment and Cmax_0-5 days and percent penetration of NMR into the CSF compared to blood.
| Animal | Cmax_0-5 days (ng/mL) Plasma | AUC0-endoftreatment (µg*hr/mL) Plasma | AUCdaily_average (µg*hr/mL) Plasma | Cmax_0-5 days (ng/mL) CSF | AUC0-endoftreatment (µg*hr/mL) CSF | AUCdaily_average (µg*hr/mL) CSF | % Penetration by Cmax CSF/Plasma | % Penetration by AUC CSF/Plasma |
|---|---|---|---|---|---|---|---|---|
| 1 | 2270 | 160 | 32 | 105.81 | 7.11 | 1.42 | 4.66 | 4.44 |
| 2 | 3660 | 189 | 37.8 | 252 | 12.5 | 2.5 | 6.89 | 6.61 |
| 3 | 2020 | 92.7 | 18.54 | 655.8 | 28.9 | 5.78 | 32.47 | 31.175 |
| 4 | 796 | 76.3 | 15.26 | 144 | 11.6 | 2.32 | 18.10 | 15.20 |
| 5 | 1860 | 80.7 | 16.14 | 1169.9 | 52.21 | 10.44 | 62.84 | 64.7 |
| 6 | 2218 | 128 | 25.6 | 560 | 30.2 | 6.04 | 25.27 | 23.59 |
| 7# | 4550 | 19.55 | 3.91 | NA | NA | NA | NA | NA |
| 8 | 3857.9 | 99.8 | 19.96 | 1107 | 28.6 | 5.72 | 28.70 | 28.66 |
| 9 | 4879.3 | 205 | 41 | 410 | 17.4 | 3.48 | 8.41 | 8.49 |
| 10 | 1862.7 | 128 | 25.6 | 271.6 | 17.6 | 3.52 | 14.58 | 13.75 |
| Median (IQR) | 2240 (1860–4030) | 113.9 (79.6–167.3) | 22.78 (15.92–33.45) | 410 (200–880) | 17.6 (12.05–29.55) | 3.52 (2.41–5.91) | 18.1 (7.65–30.59) | 15.2 (7.55–29.92) |
| Median (IQ R)* | 2220 (1860–3760) | 128 (86.7–174.5) | 25.6 (17.34–34.9) | – | – | – | – | – |
| Geometric mean*# (Geometric SD factor) | 2480 (1730) | – | 20.25 (1.956) | – | – | – | – | – |
Units for Cmax converted to ng/mL for consistency. AUC kept in µg*hr/mL.
Cmax maximum concentration, AUC area under the curve, CSF cerebral spinal fluid, T ½ half = life, IQR interquartile range, SD standard deviation.
*Excluding rat 7 as no CSF was obtained from this animal, #Calculated to compare to clinical data.