In vitro permeability and efflux data and human clearance for 16 marketed drugs
Each value represents the average of two or three determinations.
| Compounds | Compound Type | MDCK | MDR1-LLC-PK1 Cells | mBcrp-MDCK Cells | CLha | -Fold Underprediction | |||
|---|---|---|---|---|---|---|---|---|---|
| PappA-B | PappA-B | Efflux Ratio | PappA-B | Efflux Ratio | Observed | Predicted | |||
| 10−6 cm/s | 10−6 cm/s | 10−6 cm/s | ml/min/kg | ml/min/kg | |||||
| Buspirone | I | 29.8 | 35.1 | 0.8 | 29.9 | 1.2 | 19.20 | 12.11 | 1.6 |
| Clozapine | I | 13.0 | 20.9 | 0.8 | 12.3 | 0.9 | 2.90b | 1.90b | 1.5 |
| Diclofenac | I | 50.0 | 6.8 | 1.5 | 26.4 | 1.6 | 7.33 | 2.92 | 2.5 |
| Gemfibrozil | I | 39.2 | 11.4 | 1.6 | 29.9 | 1.3 | 3.09 | 1.43 | 2.2 |
| Imipramine | I | 13.8c | 22.7 | 0.8 | 11.6c | 0.9 | 9.46 | 6.30 | 1.5 |
| Metoprolol | I | 23.6 | 17.8 | 1.4 | 32.5 | 0.7 | 12.15 | 5.95 | 2.0 |
| Propafenone | I | 16.0 | 14.7 | 1.4 | 16.5 | 0.9 | 19.00b | 13.00b | 1.5 |
| Tolbutamide | I | 32.7 | 23.1 | 0.7 | 25.1 | 1.4 | 0.30 | 0.24 | 1.3 |
| Verapamil | I | 24.3 | 13.2 | 3.9 | 21.8 | 1.3 | 14.66 | 11.65 | 1.3 |
| Indomethacin | II | 20.6 | 12.3 | 2.0 | 6.9 | 7.5 | 2.24 | 0.46 | 4.9 |
| Prazosin | II | 23.6 | 4.1 | 12.1 | 2.0 | 25.2 | 2.70 | 0.45 | 6.0 |
| Ritonavir | II | 7.8d | 0.6 | 49.7 | 2.1 | 21.5 | 1.20 | 0.44 | 2.7 |
| Bosentan | III | 3.6 | 0.4 | 51.6 | 0.8 | 29.4 | 3.65 | 0.01 | 272.4 |
| Cyclosporine | III | <1cd | <1 | >5.5 | <1 | >2.8 | 4.70 | 0.52 | 9.0 |
| Montelukast | III | <1d | <1c | N.C. | <1c | N.C. | 1.27 | 0.09 | 14.1 |
| Troglitazone | III | 4.2d | 6.4 | 1.4 | 1.6c | 2.0 | 9.00 | 0.51 | 17.6 |
N.C., not calculated because of low PappB-A.
↵a As reported in Riley et al. (2005), CLh predicted from human hepatocytes.
↵b As reported in Obach (1999), CLh predicted from human liver microsomes.
↵c Recovery less than 50%.
↵d PappA-B determined in the presence of 0.1% BSA as a result of low recovery in the absence of BSA.