Table 3

Kinetic parameters for amitriptyline N-demethylation by lymphoblast-expressed CYP2C19 and CYP3A4 without and with the addition of control microsomes from untransfected lymphoblast cells

CYP IsoformParameterConcentration of Control Microsomes Added3-c
0750
μg/ml
2C193-a V max 3-c 4.22  ± 0.24.01  ± 0.3
K m 3-d 10.22  ± 1.535.8  ± 6.4
K s 3-d 766  ± 1581661  ± 702
3A43-b V max 3-c 3.09  ± 0.093.5  ± 0.11
S50 3-d 84.6  ± 4.4150.4  ± 7.9
A 1.91  ± 0.21.74  ± 0.1

Values are mean ± S.E. of parameter estimates.Km and S50 estimates are apparent values based on total (added) substrate concentrations.

  • 3-a A Michaelis-Menten model with uncompetitive substrate inhibition (eq. 1) was used.

  • 3-b A Hill enzyme model (eq. 2) was used.

  • 3-c Given in picomoles per minute per picomole of CYP.

  • 3-d Given as micromolar.

  • 3-e Active microsomal protein concentration was 250 μg/ml in all cases.