TABLE 1

Summary of CYP2C19 IC50 shift and Ki and kinact values for ticlopidine, (S)-benzylnirvanol, racemic, (S)- and (R)-fluoxetine, and racemic norfluoxetine in human liver microsomes

Values shown are results from experiments conducted in duplicate on independent days.

Compound
IC50 - NADPH
IC50 + NADPH
IC50 Shift
kinact
KI
min-1 μM
(±)-Fluoxetine 22, 37, 22 3.3, 3.9, 1.8 6.6, 9.4, 12 0.031, 0.029, 0.031 17, 11, 13
(S)-Fluoxetine 91, 79, 109 2.8, 3.3, 4.0 33, 24, 28 0.075, 0.115, 0.064 40, 54, 46
(R)-Fluoxetine 20, 22, 21 3.5, 3.9, 4.7 5.6, 5.5, 4.4 0.026, 0.024, 0.018 7.5, 6.8, 5.3
(±)-Norfluoxetine 18 1.5 11 N.D. N.D.
(S)-Benzylnirvanol 0.19, 0.16, 0.17 0.41, 0.43, 0.44 0.46, 0.38, 0.38 N.A. N.A.
Ticlopidine
1.14, 1.20, 1.43
0.81, 0.76, 0.59
1.4, 1.6, 2.4
N.D.
N.D.

  • N.A., not applicable; N.D., not done.