Summary of enzyme kinetic data for rac-propranolol, imipramine, and rac-warfarin metabolism in human liver microsomes
| Parameter | Propranolol | Imipramine | Warfarin |
|---|---|---|---|
| K Mapp(1) (μM) | 3.0 | 2.5 | 2.0 |
| V max(1) (pmol/min/mg) | 144 | 110 | 1.0 |
| Cl′int(1) (ml/min/mg) | 0.048 | 0.044 | 0.0005 |
| K Mapp(2) (μM) | ND2-a | 550 | 150 |
| V max(2) (pmol/min/mg) | ND2-a | 5100 | 121 |
| Cl′int(2) (ml/min/mg) | 0.005 | 0.009 | 0.0008 |
| Total Cl′int (ml/min/mg) | 0.053 | 0.053 | 0.0013 |
| Scaled-up Cl′int (ml/min/kg) | 48 | 48 | 1.2 |
| Corrected KM (1) (μM) | 1.1 | 0.4 | 1.5 |
| Corrected KM (2) (μM) | ND2-a | 88 | 110 |
↵2-a ND, individualKMapp and Vmax could not be determined for the high KM enzyme(s) involved in propranolol metabolism.
Cl′int was calculated asVmax/KMapp. Scale-up of Cl′int was done using values of 45 mg microsomal protein/g liver wet weight and 20 g liver wet weight per kg human body weight. Corrected KM was calculated asKMapp · fu(microsomes) using values obtained from 1.0 mg protein/ml (propranolol and imipramine at 1.0 μM) and 3.0 mg protein/ml (warfarin at 10 μM).