TABLE 2

Values of EC50, Emax, and γ (Hill slope) (± S.E.) for induction of CYP3A4 mRNA and midazolam-1′-hydroxylase activity by PF-06282999

The S.E. values reflect the fit parameter uncertainty; n = number of replicates.

PF-06282999n
DonorCYP3A4 mRNAaCYP3A4 Activitya
EC50 ± S.E.Emax ± S.E.γ ± S.E.bEC50 ± S.E.Emax ± S.E.γ ± S.E.b
μMμM
HH1089105 ± 1124.5 ± 1.271.25 ± 0.0792.1 ± 25.63.76 ± 0.341.03
HC7-456 ± 4.527.1 ± 1.282.20 ± 0.3162.3 ± 6.23.70 ± 0.141.6 ± 0.23
FOS43 ± 2.912.7 ± 0.451.99 ± 0.2475.5 ± 11.54.64 ± 0.231.03
  • a Fold induction in CYP3A4 mRNA or enzyme activity (midazolam hydroxylation) expressed as pmol/min/106 cells.

  • b Where tabulated, γ ≠ 1.0, CYP3A4 mRNA, and activity data were fit using a four-parameter sigmoidal model; otherwise data were fit using a three-parameter sigmoidal model.