Table 6

Specificity of inhibitory activity of mAbs anti-P450 2C8, 2C9, and 2C19 for phenanthrene metabolism

P450% Inhibition of Metabolism (expressed P450s)
1A11A21B12A62B62C82C9*12C9*22C182C192D62E13A43A5
Control Activity6-a 3.520.320.381.1514.40.291.410.940.041.300.681.080.610.10
mAbs anti-2C8mAb
281-1-1 —6-b 91.0
13-1-36.08.289.2
5-1-582.816.1
mAbs anti-2C9292-2-311.092.5
763-15-588.090.0 —6-c 6.6
592-2-580.690.8467.3
327-8-382.689.154
5-7-58.391.393.37492.1
1-68-1185.693.791.589.295.0
mAbs anti-2C191-7-4-86-d 6-d 97.6
1-1-117.86-d 6-d 97.5
1-5-1-36-d 6-d 97.5

Formation of 9-10 diol was measured except for 2A6, where 9-phenol was measured, and 2D6, where bufurolol was used as the substrate and 1-OH bufurolol was measured.

  • 6-a  Control activity in nanomoles per minute per nanomoles of P450.

  • 6-b  —, <1 to 5% inhibition.

  • 6-c  At very high levels mAb 763-15-5 inhibited P450 2C18 by 25% (Fig. 2A).

  • 6-d  At very high levels, mAbs anti-2C19 inhibited P450 2C9*1 by 15% and 2C9*2 by 30% (Fig. 2D).