Table 1.
Drug constants and physiological parameter values used in the final semiphysiologically based pharmacokinetic model
| Parameter | Value | References |
|---|---|---|
| S‐ketamine (SK) | ||
| f u,SK | 0.70 | 6 |
| f u,GW,SK | 1 | 41 |
| BPRATIO | 0.50 | 42 |
| f m,CYP2B6 | 0.60a | 8 |
| Norketamine (NK) | ||
| f u,NK | 0.50 | 37 |
| f u,GW,NK | 1 | 41 |
| BPRATIO | 1 | 41 |
| Ticlopidine (TIC) | ||
| f u,TIC | 0.02 | 43 |
| f u,GW,TIC | 1 | 41 |
| BPRATIO | 1 | 41 |
| k inact | 0.30 min−1 | 11 |
| K I | 0.57 μM | 11 |
| k i | 0.031 μM | 11 |
| Physiological parameters | ||
| Q H | 3.75aWTKG0.75 | 44 |
| Q PV | 0.75a Q H | 45 |
| Q HA | 0.25a Q H | 45 |
| Q INT | 0.40a Q H | 45 |
| Q MU | 0.80a Q INT | 41 |
| Q VI | 0.60a Q MU | 41 |
| V H | 1 | |
| V GW | 1 | |
| V PV | 1 | |
| k deg | 0.00026 min−1 | 43 |
BPRATIO, blood to plasma ratio; CYP, cytochrome P450; f u, unbound drug fraction in the blood; f u,GW, unbound drug fraction in the gut wall; f m,CYP2B6, fraction of drug metabolized by CYP2B6; k deg, the de novo physiological rate of degradation of CYP2B6; k i, the equilibrium dissociation constant of ticlopidine for CYP2B6; K I, the inhibitor concentration half maximal inactivation rate; K inact, maximum rate of inactivation of CYP2B6 at [I] = ∞; Q H, Q PV, Q HA, QINT, Q MU, and Q VI, are the hepatic, portal vein, hepatic artery, intestinal, mucosal, and villous blood flow, respectively. V H, V GW, and V PV are the hepatic, gut wall, and portal vein volumes.
Calculated as a parameter in the model, final value = 0.63.