TABLE 4

Median values and 95% CIs of optimized in vitro parameters (Emax and EC50) describing P450 induction due to bosentan

Assay and Hepatocyte LotaEmaxEC50
nM
CYP2B6 activity
 HC7-49.62 (8.4, 11)
 HH10251.40 (1.1, 1.7)1440 (1100, 1900)
 FOS9.13 (7.9, 11)
CYP3A4 activity
 HC7-411.0 (9.5, 13)
 HH10251.62 (1.3, 2.0)433 (320, 590)
 FOS8.26 (7.2, 9.5)
CYP2B6 mRNA
 HC7-411.1 (9.0, 14)
 HH102511.2 (9.0, 14)958 (600, 1500)
 FOS3.89 (3.0, 5.0)
CYP3A4 mRNA
 HC7-4127 (110, 150)
 HH102572.9 (60, 89)1118 (860, 1500)
 FOS29.9 (25, 36)
  • a HC7-4 and FOS are from male donors and HH1025 is from a female donor.