TABLE 1

Determination of Ki and Ks for CYP2B6dH and K262R with clinically important drugs

The inhibition was performed using a 7-MFC O-deethylation assay in a standard reconstitution system as described under Materials and Methods.


Drugs

Ki

Ks

ΔAmax
CYP2B6dH
K262R
CYP2B6dH
K262R
CYP2B6dH
K262R
μM μM
Clopidogrel 0.07, 0.12a 0.36, 0.47 0.16 ± 0.11b 0.33 ± 0.14 0.026 ± 0.002 0.030 ± 0.002
Clotrimazole 0.15, 0.11 0.11, 0.17 N.D. N.D. N.D. N.D.
Itraconazole 1.42, 1.34, 1.14 4.40, 3.84, 4.34 0.07 ± 0.13 1.73 ± 0.44 0.022 ± 0.003 0.021 ± 0.002
Raloxifene 5.59, 2.60 15.8, 17.8 N.D. N.D. N.D. N.D.
Sertraline 0.22, 0.38 1.70, 1.76 0.51 ± 0.16 2.06 ± 0.61 0.008 ± 0.0005 0.02 ± 0.002
Ticlopidine
0.11, 0.16
0.14, 0.12
0.28 ± 0.13
0.32 ± 0.11
0.023 ± 0.001
0.025 ± 0.001
  • N.D., not determined.

  • a Ki values are shown from each independent determination.

  • b Standard errors for fit to the tight ligand binding equation. The data are representative of at least two independent determinations. The variations between the experimentsare ≤20%.