TABLE 3

Prediction of Clint in human liver microsomes from enzyme kinetic parameters of lansoprazole enantiomers from cDNA-expressed P450 enzymes The predicted Clint was estimated from the nmol/mg of protein content of each P450 enzyme and the enzyme kinetic parameters shown in Table 2, obtained by incubation of expressed P450, as described under Materials and Methods.

Enzyme
CYP2C9
CYP2C19
CYP3A4
Sum Clint
R-Form
Hydroxy 0.1 1.32 0.46 1.88
Sulfone -a - 1.39 1.39
Total Clint 0.1 (3.1)b 1.32 (40.4) 1.85 (56.6) 3.27 (100)
S-Form
Hydroxy 0.75 1.65 0.35 2.75
Sulfone - - 9.86 9.86
Total Clint
0.75 (6.0)
1.65 (13.1)
10.21 (81.0)
12.61 (100)

  • ↵ a -indicates that no metabolite was detected

  • ↵ b Values in parentheses indicate the percentages of sum Clint for the formation of both metabolites by each P450 isoform from S- and R-lansoprazole