TABLE 1

In vitro reversible (IC50) and time-dependent (KI and kinact,app) inhibition constants for the enantiomers of fluoxetine and norfluoxetine in HLMs

All inhibition values are expressed as mean and standard error.

IC50KIkinact,appkinact,app/KI
μMmin−1l/min/μmol
CYP2C19
 (R)-Fluoxetine2 ± 12 ± 10.017 ± 0.0019.4
 (S)-Fluoxetine34 ± 555 ± 170.055 ± 0.0061.0
 (R)-Norfluoxetine15 ± 115 ± 30.050 ± 0.0103.3
 (S)-Norfluoxetine4 ± 17 ± 10.059 ± 0.0028.4
CYP3A4
 (R)-Fluoxetine80 ± 9NDNDND
 (S)-Fluoxetine47 ± 521 ± 190.009 ± 0.0030.5
 (R)-Norfluoxetine5 ± 18 ± 30.011 ± 0.0011.4
 (S)-Norfluoxetine11 ± 1NDNDND
  • ND, not determined.