Table 1

Correlation of various CYP-selective monooxygenase activities with the hydroxylation of ABT-761 and ABT-438 in a panel of human liver microsomes

Reaction1-aCYP Form(s)Correlation Coefficient
TOLaseCYP2C90.631-b 0.61
COHaseCYP2A60.741-c 0.731-c
DEXaseCYP2D60.601-b 0.59
ERNDaseCYP3A0.831-c 0.831-c
CYP2D61-d CYP2D60.500.49
MEPHaseCYP2C190.861-e 0.871-e
Total CYP1-f 0.921-e 0.921-e
ABT-438 hydroxylation0.991-e
Zileuton sulfoxidation (S1)CYP3A/CYP2C90.971-e 0.981-e
Zileuton sulfoxidation (S2)CYP3A/CYP2C90.971-e 0.981-e
Zileuton hydroxylationCYP1A2/CYP2C90.470.46
ABT-193 sulfoxidationCYP3A/CYP2C90.971-e 0.981-e
ABT-193 hydroxylationCYP1A2/CYP2C90.560.53
  • The correlation coefficients were determined with liver tissue from 11 different organ donor subjects, except for correlations involving tolbutamide hydroxylase (N = 10). The final concentration of ABT-761 and ABT-438 used in the analysis was 10 μM.

  • 1-a TOLase, tolbutamide hydroxylase; COHase, COU hydroxylase; ERODase, 7-ethoxyresorufin O-deethylase; DMNase,N,N-dimethylnitrosamine N-demethylase; DEXase, dextromethorphan O-demethylase; ERNDase, erythromycinN-demethylase; MEPHase, (S)-(+)-mephenytoin 4′-hydroxylase.

  • 1-b p < 0.05.

  • 1-c p < 0.01.

  • 1-d The levels of CYP2D6 apoprotein were measured using an enzyme-linked immunosorbent assay procedure.

  • 1-e p < 0.001.

  • 1-f Total (spectrally detectable) CYP.