Effect of DDB on P450 isoform-specific marker activities in human liver microsomes
| DDB | Coumarin 7-Hydroxylation | Caffeine N-Demethylation | Chlorzoxazone 6-Hydroxylation | S-Mephenytoin 4′-Hydroxylation | Testosterone 6β-Hydroxylation | Diclofenac 4′-Hydroxylation | Dextromethorphan O-Demethylation |
|---|---|---|---|---|---|---|---|
| 0 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| 0.25 | —1-a | — | — | — | 71 | — | — |
| 0.5 | — | — | — | — | 37 | — | — |
| 1 | 99 | 98 | 102 | 99 | 27 | 101 | 94 |
| 5 | 91 | 81 | 111 | 103 | 7 | 91 | 86 |
| 10 | 104 | 85 | 99 | 98 | — | 96 | 84 |
| 25 | 101 | 84 | 95 | 97 | — | 85 | 67 |
| 50 | 93 | 75 | 96 | 87 | — | 72 | 51 |
Percentage of remaining P450 activity was calculated after incubation with various concentrations of DDB and substrates in the presence of 0.5 mg/ml of pooled human liver microsomal protein and NADPH-generating system at 37°C. The uninhibited rates of the reactions were 0.441 nmol/min/mg of protein for coumarin 7-hydroxylation, 92 pmol/min/mg of protein for caffeine N-demethylation, 0.456 nmol/min/mg of protein for chlorzoxazone 6-hydroxylation, 13.6 pmol/min/mg of protein for S-mephenytoin 4′-hydroxylation, 0.521 nmol/min/mg of protein for testosterone 6β-hydroxylation, 0.122 nmol/min/mg of protein for diclofenac 4′-hydroxylation, and 18.1 pmol/min/mg of protein for dextromethorphan O-demethylation. Each data represents the mean of two independent experiments.
↵1-a —, not examined.