TABLE 2

In vitro inhibitory parameters of OMP and metabolites for CYP2C19 and CYP3A4

N.D., not determined. Data are shown as means ± S.D. (n = 3).

Target P450InhibitorIn Vitro Parameters
fu,m(0.1)afu,m(1.0)aIC50KIkinactkinact/KI
µMµMmin−1L∙min−1µmol−1
CYP2C19OMP0.98 ± 0.060.92 ± 0.048.4 ± 0.68.2 ± 3.60.029 ± 0.0040.0035
OH-OMP0.95 ± 0.060.93 ± 0.0539 ± 2N.D.N.D.N.D.
DM-OMP1.0 ± 0.11.0 ± 0.131 ± 28.7 ± 4.30.020 ± 0.0030.0022
OMP-S0.96 ± 0.020.89 ± 0.055.1 ± 0.25.7 ± 0.80.015 ± 0.0010.0026
COMP0.98 ± 0.050.98 ± 0.05> 50N.D.N.D.N.D.
CYP3A4OMP0.98 ± 0.060.92 ± 0.0440 ± 452 ± 80.029 ± 0.0010.0006
OH-OMP0.95 ± 0.060.93 ± 0.0521 ± 4N.D.N.D.N.D.
DM-OMP1.0 ± 0.11.0 ± 0.115 ± 461 ± 150.086 ± .0100.0014
OMP-S0.96 ± 0.020.89 ± 0.058 ± 1N.D.N.D.N.D.
COMP0.98 ± 0.050.98 ± 0.0548 ± 6N.D.N.D.N.D.
  • a fu,m(0.1) and fu,m(1.0) are the microsomal unbound fractions of OMP and its metabolites for 0.1 mg/mL and 1.0 mg/mL HLMs, respectively.