Table 2

Mean kinetic parameters for the formation of (S)-7-hydroxy warfarin, 4′-hydroxy diclofenac, and 11-hydroxy lauric acid by CYP2C9 variants. Metabolic incubations were carried out in duplicate and kinetic parameters were obtained as detailed under Materials and Methods. Duplicate velocity measurements varied less than 10% from the average when using (S)-warfarin and diclofenac as substrates, and by less than 18% for lauric acid incubations.

(S)-WarfarinDiclofenacLauric Acid
KmVmaxVmax/KmKmVmaxVmax/KmKmVmaxVmax/Km
μM nmol of product/nmol of P450/min ml/nmol of P450/min μM nmol of product/nmol of P450/min ml/nmol of P450/min μM nmol of product/nmol of P450/min ml/nmol of P450/min
CYP2C9*15.60.140.0254.8296.04344.30.127
CYP2C9*3280.020.00117130.761250.80.006
CYP2C9*5670.140.00222251.14961.10.012