Table 1.
Parameters required for a drug file to inform the physiologically‐based pharmacokinetic model
| Parameter | Typical units | Explanation |
|---|---|---|
| Physicochemical properties | ||
| MW | g/mol | Molecular weight |
| logP | – | Octanol‐water partition coefficient |
| Compound type | – | Important property to predict tissue distribution according to Rodgers and Rowland |
| pKa | – | Acid dissociation constant |
| BP | – | Blood‐to‐plasma ratio |
| fuPL | – | Fraction unbound in plasma |
| Absorption | ||
| P app | ×10−6 cm/s | Apparent permeability |
| Distribution | ||
| Kp scalar | – | Scalar to alter predicted partition coefficient |
| Elimination | ||
| V max/K m or CLint | pmol/minute/pmol enzyme/μM or μmol/minute/mg protein | Kinetic parameters per enzyme and metabolic pathway |
| CLr | L/h | Renal clearance |
| CLad | L/h | Additional plasma clearance |
| Transporter | ||
| CLpd | μL/minute/Mio cells | Passive diffusion flux |
| V max/K m or CLint | pmol/minute/pmol transporter/μM or μmol/minute/Mio cells | Kinetic parameters for transporters |
| Interactions | ||
| K i | μM | Inhibition constant for competitive inhibition |
| K app | μM | Apparent enzyme inhibition constant for mechanism‐based inhibition |
| k inact | 1/h | Maximum inactivation rate constant |
| IndMax | – | Maximum fold of induction |
| IC50 | μM | Half maximum inhibitory concentration |