TABLE 1

Apparent Michaelis-Menten kinetic parameters for dextromethorphan and codeine O-demethylation catalyzed by CYP2D6 allelic isoforms

Values are mean ± S.E.M. of triplicate incubations at 37° C for 5 (DXM) or 30 min (codeine). DXM and codeine concentrations ranged from 0 to 30 and 0 to 4000 μM, respectively. Metabolites were quantified by HPLC with fluorescence detection. Kinetic parameters, Km and Vmax, were estimated by nonlinear regression.

Reaction
Allelic isoform
Km
Vmax
CLint
μM pmol/pmol P450/min μl/pmol P450/min
DXM CYP2D6.1 0.60 ± 0.17 0.73 ± 0.04 1.22
CYP2D6.24 0.68 ± 0.07 4.78 ± 0.09* 7.03
O-Demethylation CYP2D6.26 3.93 ± 0.24* 2.98 ± 0.06* 0.76
CYP2D6.27 1.45 ± 0.33* 0.63 ± 0.03 0.43
Codeine CYP2D6.1 13.0 ± 4.4 0.79 ± 0.04 0.061
CYP2D6.24 37.3 ± 7.8* 1.24 ± 0.06 0.033
O-Demethylation CYP2D6.26 26.7 ± 11.4 2.37 ± 0.21* 0.087
CYP2D6.27
10.9 ± 2.3
0.95 ± 0.03
0.089

  • ↵* Significantly different from the corresponding value for CYP2D6.1.