TABLE 3

Comparison of metabolic stabilities of AO substrates in incubations with HLM fortified with NADPH and human hepatocytes

CompoundMean CLint,liver ± S.E. 
(ml/min per kilogram BW)a
MicrosomesHepatocytesFold Difference
A77-0152 ± 2198 ± 23.8
Bafetinib33 ± 187 ± 82.7
Carbazeran28 ± 3208 ± 27.4
CL-38778531 ± 7124 ± 314.0
Duvalisib25 ± 110 ± 0.4BQL (0.4)b
Imatinib21 ± 0.059 ± 0.7BQL (0.4)b
INCB2806026 ± 517 ± 0.1BQL (0.6)b
Lapatinib14 ± 415 ± 1BQL (1.1)b
Lapatinib M110 ± 339 ± 0.83.8
LDN-19318916 ± 0.872 ± 54.6
Midazolam127 ± 1249 ± 1.3BQL (0.4)b
ML-34717 ± 0.254 ± 0.13.2
SB-5253446 ± 0.146 ± 0.087.8
VX-50947 ± 0.415 ± 2BQL (0.3)b
Zoniporide4 ± 0.639 ± 0.69.2
  • BQL, below the quantitation limit (1.5-fold in this assay).

  • a n = 2.

  • b Human hepatocyte/HLM CLint ratio in parentheses.