Table 2.
Drug-specific parameters
| Drug | Molecular weight | Charge class | pKa | pKb | logP | Kpuu,ECF | AFin,ECF | AFout,ECF | Kpuu,LV | AFin,LV | AFout,LV | Kpuu,CM | AFin,CM/SAS | AFout,CM/SAS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acetaminophen | 151.16 | Neutral | 9.46 | − 4.4 | 0.46 | 0.51a | 1 | 12.5 | 0.51a | 1 | 86.8 | 0.51a | 1 | 90 |
| 1b | 1 | 1 | 1b | 1 | 1 | 1b | 1 | 1 | ||||||
| Atenolol | 266.34 | Base | 14.08 | 9.67 | 0.16 | 0.037a | 1 | 9.9E4 | 0.037a | 1 | 8.3E5 | 0.037a | 1 | 8.3E5 |
| Indomethacin | 357.8 | Acid | 3.79 | − 2.9 | 4.27 | 0.1c | 1 | 5.7 | 0.272g | 1 | 47.3 | 0.272g | 1 | 48.1 |
| Methotrexate | 454.45 | Acid | 3.41 | 2.81 | − 1.85 | 0.018a | 1 | 4.1E8 | 0.0066a | 1 | 9.5E9 | 0.0024a | 1 | 2.6E10 |
| Morphine | 285.34 | Base | 10.26 | 9.12 | 0.87 | 0.38a, d | 1 | 372.8 | 0.38a, d | 1 | 2999.5 | 0.38a, d | 1 | 3088.1 |
| 0.23a, e | 1 | 764.5 | 0.23a, e | 1 | 6248 | 0.23a, e | 1 | 6336.6 | ||||||
| 0.23f | 1 | 170.4 | 0.23f | 1 | 671.8 | 0.23f | 1 | 677.2 | ||||||
| Oxycodone | 315.37 | Base | 13.56 | 8.21 | 0.7 | 1.69f | 17.6 | 1 | 2g | 100.6 | 1 | 2g | 94.7 | 1 |
| Paliperidone | 426.49 | Base | 13.74 | 8.76 | 1.8 | 0.5a | 1 | 13.7 | 0.5a | 1 | 90.8 | 0.5a | 1 | 96 |
| Phenytoin | 252.27 | Neutral | 9.47 | − 9 | 2.47 | 0.26a | 1 | 4.2 | 0.26a | 1 | 6.5 | 0.26a | 1 | 6.5 |
| Quinidine | 324.42 | Base | 13.89 | 9.05 | 3.44 | 1.5a | 1.5 | 1 | 1.5a | 3.9 | 1 | 1.5a | 3.6 | 1 |
| Raclopride | 347.24 | Amphoteric | 5.31 | 9.32 | 3.38 | 1.1a | 16 | 1 | 1.1a | 187.2 | 1 | 1.1a | 120.5 | 1 |
| Remoxipride | 371.28 | Base | 13.06 | 8.4 | 2.1 | 0.8a | 1 | 2.2 | 0.8a | 1 | 6.2 | 0.8a | 1 | 7.5 |
| Risperidone | 410.49 | Base | NA | 8.76 | 3.27 | 0.97a | 1 | 1.3 | 0.97a | 1 | 1.2 | 0.97a | 1 | 1.4 |
aValues are measured in rats
bAssumed value based on physiological knowledge, used for human predictions[7]
cValues are measured in rats and corrected for human translation as described in [7]; indomethacin is MRP4 [63], MRP6 [64], OAT1[65], OAT3 [66] substrate. Expression levels of these transporters are at least eightfold lower in humans than in rats [67–69]. No information on interspecies differences of transporter activity could be identified and was then assumed the same. Thus, AF factors were calculated using rat values and then divided by scaling factor = 8
dDose: 4 mg/kg
eDose: 10, 40 mg/kg
fValues are measured in rats and corrected for human translation as described in[7]
gValues measured in humans