TABLE 1 

Emax and EC50 values for mRNA and activity of metabolic enzymes and transporters after multiple treatment with RO6889678 for 4 and 10 days in HepatoPac

Data are the mean of three determinations ± S.E.

Metabolic enzymes/transportersDay 4Day 10Day 4/Day 10 Ratio
EmaxEC50HillEmaxEC50HillEC50
mRNA
 CYP1A2NDNDND2.7 ± 0.11.7 ± 0.51
 CYP3A43.4 ± 0.10.11 ± 0.031.1 ± 0.39.1 ± 0.40.05 ± 0.010.91 ± 0.22.2
 CYP2B66.7 ± 0.50.59 ± 0.23113 ± 0.50.23 ± 0.051.2 ± 0.42.6
 CYP2C82.6 ± 0.10.17 ± 0.1013.9 ± 0.40.06 ± 0.031.1 ± 0.42.8
 CYP2C92.6 ± 0.10.12 ± 0.1014.8 ± 0.30.06 ± 0.031.4 ± 0.62.2
 CYP2D6NDNDNDNDNDNDND
 FMO3NDNDND3.4 ± 0.10.08 ± 0.011
 FMO4NDNDND2.7 ± 0.10.05 ± 0.011
 FMO5NDNDND2.5 ± 0.10.09 ± 0.021
 UGT1A1NDNDNDNDNDNDND
 UGT1A3NDNDNDNDNDNDND
 ABCG2 (BCRP)NDNDND2.9 ± 0.20.09 ± 0.040.73 ± 0.20
 SLC10A1 (NTCP)NDNDNDNDNDNDND
 ABCB1 (P-gp)NDNDNDNDNDNDND
 OATP1B1NDNDND3.6 ± 0.20.06 ± 0.031.4 ± 0.6
 OATP1B3NDNDND2.8 ± 0.10.16 ± 0.021.3 ± 0.3
Activity
 CYP3A42.5 ± 0.10.013 ± 0.00614.7 ± 0.10.023 ± 0.0031.2 ± 0.30.6
 CYP2B615 ± 1.40.38 ± 0.21116 ± 1.10.22 ± 0.1011.7
 CYP2C92.3 ± 0.10.040 ± 0.02012.5 ± 0.20.060 ± 0.04710.7
 CYP1A22.3 ± 0.140.014 ± 0.01413.8 ± 0.20.050 ± 0.0301.1 ± 0.460.3
 CYP2C84.0 ± 0.20.55 ± 0.160.92 ± 0.204.8 ± 0.10.13 ± 0.031.1 ± 0.24.2
  • ND, no induction (<2-fold); curves could not be fit to a sigmoidal Emax model).