TABLE 1

Final concentrations of primary metabolites and MI complexes formed from desipramine, (S)-fluoxetine, and N-desmethyldiltiazem

The concentrations of the three products, primary amine, secondary hydroxylamine, and MI complex, from incubations with 100 μM DES, 10 μM FLX, 10 μM MA, and 100 μM DES-d3. The concentration of enzyme in each experiment was 0.10 μM, except for CYP3A4 for which the concentration was 0.25 μM. Numbers in parentheses are the S.D. of triplicate experiments or S.E. of the ratios.

Substrate/EnzymePrimary AmineSecondary HydroxylamineMI ComplexMRaBRb
μMμMμM
Desipramine/CYP2C110.89 (0.10)0.23 (0.01)0.08 (0.01)3.9 (0.5)2.9 (0.4)
(S)-Fluoxetine/CYP2C190.50 (0.01)0.030 (0.001)0.11 (0.01)17 (1)3.6 (0.4)
N-Desmethyldiltiazem/CYP3A40.23 (0.02)0.10 (0.01)0.19 (0.01)2.4 (0.3)0.80 (0.09)
Desipramine-methyl-d3/CYP2C110.40 (0.04)0.27 (0.02)0.07 (0.02)1.5 (0.2)1.2 (0.4)
  • a Metabolite ratio (MR): primary amine/secondary hydroxylamine.

  • b Branching ratio (BR): primary amine/(secondary hydroxylamine + MI complex).