Table 3.
VX-765 and VRT-043198 are detected in the CSF after a single IP dose of VX-765.
| Time (h) | Mouse 1 VX-765 (μM) | Mouse 2 VX-765 (μM) | Mouse 1 VRT-043198 (μM) | Mouse 2 VRT-043198 (μM) | Mean VX-765 (μM)(a) | Mean VRT-043198 (μM)(b) |
|---|---|---|---|---|---|---|
| 0.25 | 0.21* | 0.45 | 82.6* | 3.11 | 0.33 | 42.9 |
| 0.50 | 0.07 | 1.17 | 0.44 | 7.00 | 0.62 | 3.72 |
| 1 | 0.06 | 0.10 | 0.43 | 0.58 | 0.08 | 0.50 |
| 3 | 0.07* | 0.04* | 0.42* | 0.15* | 0.06 | 0.28 |
| 6 | 0.05* | 0.06* | NQ* | 0.21* | 0.06 | 0.21 |
| 8 | 0.07* | 0.13* | 0.13* | 0.60* | 0.10 | 0.36 |
| 24 | NQ | NQ* | NQ | NQ* | − | − |
| Cmax (μM)(c) | 0.21 | 1.17 | 82.6 | 7.00 | 0.69 | 44.8 |
| Tmax (h)(d) | 0.25 | 0.50 | 0.25 | 0.5 | 0.38 | 0.38 |
| Half-life (t1/2) (h)(e) | NC | NC | NR | NC | − | − |
| MRTinf (h)(f) | NC | NC | 0.81 | NC | − | 0.81 |
NQ: not quantifiable. No peak of below lower limit of quantification: 0.006 μM for VX-765 and 0.068 μM for VRT-043198.
NC: not calculated due to shape of PK curve.
NR: not reported. The span of the terminal phase is too short to allow for accurate estimation of half-life.
*Some blood contamination during CSF collection.
Individual data points showing VX-765 and VRT-043198 concentrations up to 24 h post-injection (n = 2 per time point). (a) VX-765 and (b) VRT-043198 mean concentrations at each time point. (c) Maximum concentration achieved (Cmax), (d) time to reach Cmax (Tmax), (e) half-life (t1/2) and (f) mean residence time (MRT) in the CSF for VX-765 and VRT-043198.