Table 6. Summary of Pharmacokinetic Parameters for (P)-14 and (P)-19 in Preclinical Species.
| Parameter | Sprague–Dawley rat | Beagle dog | Cynomolgus monkey | Rhesus monkey |
|---|---|---|---|---|
| SUMMARY FOR (P)-14a | ||||
| PPB (% bound)b | 84 | 86 | 84 | 81 |
| CLpr (L/h/kg)c | 1.65 | 0.27 | 0.25 | 0.81 |
| CL (L/h/kg)d | 1.97 | 0.34 | 0.25 | 0.47 |
| Vss (L/kg)e | 2.5 | 2.5 | 1.3 | 2.6 |
| Terminal t1/2 (h)f | 1.2 | 5.5 | 4.1 | 4.4 |
| MRT (h)g | 1.3 | 7.3 | 5.2 | 5.5 |
| F (%)h | 53 | 76 | 35 | ND |
| SUMMARY FOR (P)-19a | ||||
| PPB (% bound)b | 81 | 92 | 94 | 93 |
| CLpr (L/h/kg)c | 0.60 | 0.47 | 0.22 | 0.41 |
| CL (L/h/kg)d | 0.68 | 0.22 | 0.13 | 0.10 |
| Vss (L/kg)e | 2.7 | 0.9 | 0.5 | 0.6 |
| Terminal t1/2 (h)f | 9.6 | 3.6 | 5.2 | 6.0 |
| MRT (h)g | 3.9 | 4.0 | 4.3 | 6.2 |
| F (%)h | 60 | ND | 64 | ND |
a
Intravenous doses of 1 mg/kg.
b
Plasma protein binding.
c
Predicted clearance from hepatocytes.
d
In vivo clearance.
e
Volume of distribution at steady state.
f
Half-life intravenous.
g
Mean residence time intravenous.
h
Bioavailability calculated after oral doses of 5 mg/kg. ND = value not determined.