In vitro oxidation of DTZ by cDNA-derived human P450s
| P450 | P450 content | DTZ metabolite | 7-Ethoxycoumarin metabolite |
|---|---|---|---|
| N-Desmethylated DTZ | 7-Hydroxycoumarin | ||
| pmol P450/mg of microsomal protein | pmol/hr/pmol of P450 | ||
| 1A1 | 104 | <0.05 | 16 |
| 1A2 | 147 | <0.05 | 6.1 |
| 2A6 | 103 | <0.05 | 32 |
| 2B6 | 130 | <0.05 | 23 |
| 2C8 | 26 | 2.03 | 0.42 |
| 2C9 | 34 | 1.02 | 0.25 |
| 2D6 | 217 | 0.81 | 4.4 |
| 2E1 | 188 | 0.06 | 17 |
| 3A4 | 56 | 9.92 | 23 |
| 4A11 | 40 | <0.05 | N.D. |
Cell microsomes containing individual cDNA-derived P450s were assayed for DTZ and 7-ethoxycoumarin oxidation as described in the text. Results have been corrected for background rates of substrate oxidation.
Substrate concentrations were DTZ (100 μM) and 7-ethoxycoumarin (400 μM). N.D., not determined.