TABLE 1

Summary of clomethiazole (CMZ) inhibition parameters for CYP2E1, CYP2A6, and CYP2B6a

EnzymeIC50 ValueKi Value IC50 Value, 10-min PreincubationbIC50 Value, 30-min Preincubationb
CYP2E1µMµMµMµM
42 ± 8.921 ± 1.70.96 ± 0.271.03 ± 0.22
CYP2A624 ± 4.8NDND19 ± 5
CYP2B6>300cNDND> 30d
  • ND, not done.

  • a Each value represents the mean ± S.D. of 4 (CYP2E1, IC50 value with and without 30 minutes of preincubation) or range of two (all other conditions) independent experiments.

  • b Preincubation of CMZ with human liver microsomes (HLMs) and NADPH. Preincubation of CMZ at concentrations up to 100 µM with HLMs in the absence of NADPH for 10 or 30 minutes before the addition of 60 µM chlorzoxazone substrate yielded IC50 values > 10 µM (the concentration of CMZ after 10-fold dilution), with maximum inhibition of 25%.

  • c 45 ± 0.8 (n = 2) percent inhibition was observed at 300 µM.

  • d 42 ± 4 (n = 2) percent inhibition was observed at 30 µM (the concentration of CMZ after 10-fold dilution).