Table 2

Summary of enzyme kinetic data for rac-propranolol, imipramine, and rac-warfarin metabolism in human liver microsomes

K Mapp(1) (μM)
V max(1) (pmol/min/mg)1441101.0
Cl′int(1) (ml/min/mg)0.0480.0440.0005
K Mapp(2) (μM)ND2-a 550150
V max(2) (pmol/min/mg)ND2-a 5100121
Cl′int(2) (ml/min/mg)0.0050.0090.0008
Total Cl′int (ml/min/mg)0.0530.0530.0013
Scaled-up Cl′int (ml/min/kg)48481.2
Corrected KM (1) (μM)
Corrected KM (2) (μM)ND2-a 88110
  • 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).