Table 1.

Inhibitory potency of INH for CYP450 isoformsa

Substrate reaction probeCYP450 isoformKi , μM (SD)Mechanism of inhibition
S-Mephenytoin 4-hydroxylationCYP2C1913 (2.4)Competitive
Omeprazole 5-hydroxylationCYP2C1925.4 (6.20)Competitive
Omeprazole sulfone formationCYP3A51.8 (2.5)Noncompetitive
Midazolam 4-hydroxylationCYP3A75.9 (7.8)Noncompetitive
Chlorzoxazone 6-hydroxylationCYP2E1110 (33)Noncompetitive
Dextromethorphan O-demethylationCYP2D6126 (23)Competitive
Phenacetin O-deethylationCYP1A2>1,000
Tolbutamide 4-methylhydroxylationb CYP2C9102 (17)Noncompetitive
Flurbiprofen 4′-hydroxylationCYP2C9>500Noncompetitive
Dextromethorphan N-demethylationCYP3A474 (103)Competitive
  • a To calculate the inhibition constants (Ki values) for each isoform, data obtained from three HLMs to construct Dixon plots were fitted to an appropriate nonlinear regression enzyme inhibition model. The mechanism of inhibition was decided graphically and from the enzyme inhibition models (see Materials and Methods).

  • b In recombinant CYP2C9.