In Vivo Observed Pharmacokinetic Parameters | Predicted Clearance in MPCCs | ||||||||
---|---|---|---|---|---|---|---|---|---|
fu = Reported Literature Values | fu = 1 | ||||||||
Compound Name | Known Routes of Metabolism | In Vivo Clearance | fu | Donor 1 | Donor 2 | Average | Donor 1 | Donor 2 | Average |
ml/min per kilogram | ml/min per kilogram | ||||||||
Verapamil | CYP3A4, 2C9 | 19.5 | 0.10 | 6.79 | 6.86 | 6.83 | 17.36 | 17.41 | 17.39 |
Sumatriptan | 19 | 0.83 | 12.36 | 13.74 | 13.05 | 13.29 | 14.60 | 13.95 | |
Naloxone | UGT2B7 | 18 | 0.54 | 14.45 | 14.52 | 14.49 | 16.87 | 16.92 | 16.90 |
Propranolol | CYP2D6, 1A2 | 15.7 | 0.13 | 6.70 | 4.95 | 5.83 | 16.44 | 14.77 | 15.61 |
Metoprolol* | CYP2D6 | 13 | 0.88 | 3.80 | 5.76 | 4.78 | 4.29 | 5.37 | 4.83 |
Triprolidine* | 13 | 0.50 | 3.30 | 7.78 | 5.54 | 5.70 | 11.35 | 8.52 | |
Desipramine* | CYP2D6, 1A2; UGT | 10.3 | 0.16 | 2.25 | 2.39 | 2.32 | 8.99 | 9.34 | 9.16 |
Timolol | CYP2D6 | 10.1 | 0.90 | 5.39 | N/A | 5.39 | 5.82 | N/A | 5.82 |
Dextromethorphan | CYP2D6, 3A4, 1A2, 2C19 | 8.6 | 0.50 | 10.66 | 11.39 | 11.03 | 14.14 | 14.77 | 14.46 |
Omeprazole | CYP2C19, 3A4 | 8.4 | 0.05 | 2.53 | 2.47 | 2.50 | 15.38 | 15.26 | 15.32 |
Imipramine* | CYP2D6, 1A2, 2C19, 3A4; UGT1A4 | 8 | 0.10 | N/A | 2.06 | 2.06 | N/A | 10.93 | 10.93 |
Diclofenac | CYP2C9 | 7.6 | 0.01 | 0.08 | N/A | 0.08 | 8.90 | N/A | 8.90 |
Zolmitriptan | CYP1A2 | 6.7 | 0.75 | 1.94 | 3.01 | 2.48 | 2.51 | 3.83 | 3.17 |
Methylprednisolone | CYP3A4 | 6.1 | 0.23 | 4.67 | 6.57 | 5.62 | 11.64 | 13.95 | 12.80 |
Erythromycin | CYP3A4 | 5.6 | 0.10 | 0.71 | 1.06 | 0.89 | 5.44 | 7.30 | 6.37 |
Ziprasidone | CYP3A4 | 5.1 | 0.00 | 0.10 | 0.10 | 0.10 | 16.66 | 16.63 | 16.65 |
Betaxolol* | 4.8 | 0.40 | 0.83 | 0.21 | 0.52 | 4.20 | 3.15 | 3.67 | |
Prednisolone* | CYP3A4 | 2.9 | 0.25 | 0.68 | 0.59 | 0.64 | 3.36 | 3.08 | 3.22 |
Furosemide* | 1.7 | 0.01 | 0.03 | 0.04 | 0.04 | 2.51 | 2.74 | 2.63 | |
Theophylline | CYP1A2 | 1.1 | 0.41 | 0.34 | 0.26 | 0.30 | 0.81 | 0.62 | 0.72 |
Lorazepam | UGT | 1 | 0.09 | 0.46 | 0.43 | 0.45 | 4.15 | 3.97 | 4.06 |
Diazepam | CYP2C19, 1A2, 3A4 | 0.53 | 0.02 | 0.21 | 0.22 | 0.22 | 6.30 | 6.69 | 6.50 |
Tolbutamide | CYP2C9, 2C19 | 0.38 | 0.05 | 0.21 | 0.40 | 0.31 | 3.49 | 5.84 | 4.67 |
Naproxen | CYP2C9, 1A2 | 0.19 | 0.01 | 0.18 | 0.49 | 0.34 | 9.75 | 14.78 | 12.27 |
Meloxicam | CYP2C9, 3A4 | 0.12 | 0.01 | 0.01 | 0.03 | 0.02 | 1.38 | 3.98 | 2.68 |
Warfarin* | CYP2C9, 3A4 | 0.05 | 0.02 | 0.04 | 0.02 | 0.03 | 1.85 | 1.02 | 1.44 |
Within 2-fold | 32% | 25% | 31% | 60% | 63% | 62% | |||
Within 3-fold | 48% | 58% | 58% | 68% | 71% | 73% | |||
Within 4-fold | 64% | 71% | 69% | 76% | 79% | 77% |
UGT, uridine 5′-diphospho-glucuronosyltransferase.