TABLE 5.
The pharmacokinetic parameters of (+)-9-trifluoroethoxy-α-dihydrotetrabenazine [(+)-13e], valbenazine (VBZ), and its active metabolite (+)-α-dihydrotetrabenazine (HTBZ) in dog plasma after a single oral dose at 3 μmol/kg (n = 4) and single intravenous dose of 0.6 μmol/kg (n = 3).
| Parameters | Oral | Intravenous | ||||
|---|---|---|---|---|---|---|
| (+)-13e | VBZ | HTBZ | (+)-13e | VBZ | HTBZ | |
| Tmax (h) | 0.75 ± 0.43 | 1.4 ± 0.8 | 3.3 ± 0.6 | 0.083 ± 0 | 0.083 ± 0 | 0.83 ± 0.3 |
| C0, Cmax (nM) | 507 ± 98 | 1,465 ± 461 | 66.1 ± 58.7 | 382 ± 148 | 747 ± 118 | 14.1 ± 5.1 |
| AUClast (h·nM) | 1,610 ± 386 | 6,224 ± 1,074 | 524 ± 475 | 424 ± 15.8 | 1,679 ± 365 | 61.1 ± 21.4 |
| AUCinf (h·nM) | 1,680 ± 394 | 6,385 ± 1,101 | 607 ± 532 | 441 ± 20.7 | 1722 ± 384 | 76.8 ± 24.2 |
| V, V/F (L/kg) | 18.8 ± 9.2 | 3.5 ± 0.8 | - | 5.4 ± 1.1 | 2.8 ± 0.5 | |
| Cl, Cl/F (L/kg/h) | 1.9 ± 0.4 | 0.48 ± 0.08 | - | 1.4 ± 0.1 | 0.36 ± 0.07 | |
| T1/2 (h) | 6.8 ± 2.0 | 5.1 ± 0.8 | 5.3 ± 2.6 | 2.8 ± 0.7 | 5.5 ± 1.3 | 2.8 ± 0.3 |
Tmax: time to Cmax; C0: initial concentration after intravenous administration; Cmax: peak concentration; AUClast: area under the concentration-time curve from time zero to the last measurement; AUCinf: area under the concentration-time curve from time zero to infinity; V: apparent distribution volume; Cl: clearance; F: bioavailability; T1/2: terminal elimination half-life.