Predicted drug clearance rates in MPCCs compared with suspension cultures created using the same donor (RTM)
MPCCs were stabilized for 7 days prior to dosing with drugs for up to 7 days, while suspension hepatocytes were used immediately following thawing for incubation up to 4 hours with drugs. The dash indicates that the drug did not turn over sufficiently in the model system to predict a clearance rate.
| In Vivo Observed Pharmacokinetic Parameter Values | Predicted Clearance | |||||
|---|---|---|---|---|---|---|
| fu = Reported Literature Values | fu = 1 | |||||
| Compound Name | In Vivo Clearance | fu | MPCCs | Suspension | MPCCs | Suspension |
| ml/min per kilogram | ml/min per kilogram | |||||
| Verapamil | 19.5 | 0.10 | 6.79 | 1.23 | 17.36 | 8.03 |
| Naloxone | 18 | 0.54 | 14.45 | 11.12 | 16.87 | 14.19 |
| Timolol | 10.1 | 0.90 | 5.39 | 4.66 | 5.82 | 5.06 |
| Methylprednisolone | 6.1 | 0.23 | 4.67 | — | 11.64 | — |
| Erythromycin | 5.6 | 0.10 | 0.71 | — | 5.44 | — |
| Theophylline | 1.1 | 0.41 | 0.34 | — | 0.81 | — |
| Lorazepam | 1 | 0.09 | 0.46 | — | 4.15 | — |
| Diazepam | 0.53 | 0.02 | 0.21 | — | 6.3 | — |
| Tolbutamide | 0.38 | 0.05 | 0.21 | — | 3.49 | — |
| Naproxen | 0.19 | 0.01 | 0.18 | — | 9.75 | — |
| Within 2-fold | 50% | 10% | 60% | 20% | ||
| Within 3-fold | 80% | 20% | 60% | 30% | ||
| Within 4-fold | 90% | 20% | 60% | 30% | ||