Table 1

Prediction of CLint in human liver microsomes from enzyme kinetic parameters from cDNA-expressed enzymes for S-omeprazole

EnzymeCYP2C19CYP2C9CYP3A4CYP2A6CYP2D6Total CLint
μl/min · mg
Sulfone20.620.6
5-O-desmethyl13.60.600.360.0214.6
Hydroxy1.500.670.750.020.053.34
ΣCLint 15.11.2721.70.020.0738.2
% of total CLint 403.3570.050.18

The percentage of each P450 in human liver microsomes was estimated to be: CYP2C19 2% (Yamazaki et al., 1997), CYP2C9 18%, CYP3A4 28%, Cyp2A6 4%, and CYP2D6 1.5% (Shimada et al., 1994). Total CYP content in a typical preparation is 0.46 nmol/mg of microsomal protein. The nanomole per milligram of protein content of each CYP enzyme was therefore estimated to be: CYP2C19: 0.0092, CYP2C9: 0.083, CYP3A4: 0.129, CYP2A6: 0.018, and CYP2D6: 0.0069. These values were used to predict CLint in human liver microsomes from the CLint values in Tables 4 and 5 obtained by using expressed enzymes.

  • —, indicates that no metabolite was detected.