Selected compounds | APD | ||||||
---|---|---|---|---|---|---|---|
Properties | Parameters | Measurement | 1 | 2 | 8 | 16 | Donepezil |
Absorption | Water solubility | Numeric (log mol/L) | − 2.399 | − 1.706 | − 2.011 | − 3.907 | − 4.632 |
CaCO2 permeability | Numeric (log Papp in 10–6 cm/s) | 0.043 | 1.186 | − 0.111 | − 0.428 | 1.321 | |
Intestinal absorption (human) | Numeric (% Absorbed) | 89.051 | 94.978 | 83.024 | 83.014 | 92.768 | |
Skin Permeability | Numeric (log Kp) | − 2.79 | − 2.962 | − 2.601 | − 2.743 | − 2.647 | |
Distribution | VDss (human) | Numeric (log L/kg) | − 0.202 | 0.167 | − 0.16 | − 0.229 | 1.179 |
Fraction unbound (human) | Numeric (Fu) | 0.214 | 0.427 | 0.256 | 0.049 | 0.01 | |
BBB permeability | Numeric (log BB) | − 0.633 | − 0.197 | − 0.673 | − 1.69 | 0.479 | |
CNS permeability | Numeric (log PS) | − 2.637 | − 2.297 | − 2.622 | − 3.116 | − 1.445 | |
Metabolism | CYP3A4 substrate | Categorical (yes/no) | Yes | Yes | Yes | Yes | Yes |
Excretion | Total clearance | Numeric (log ml/min/kg) | 0.367 | 0.162 | 0.366 | 0.464 | 0.994 |
Toxicity | AMES toxicity | Categorical (yes/no) | Yes | Yes | Yes | Yes | No |
Max. tolerated dose (human) | Numeric (log mg/kg/day) | 0.187 | 0.082 | 0.156 | − 1.149 | − 0.171 | |
Hepatotoxicity | Categorical (yes/no) | No | No | No | No | Yes | |
Skin sensitisation | Categorical (yes/no) | No | No | No | No | No |