Effects of various P450 substrates and inhibitors on bropirimine metabolism by pooled human liver microsomes
| Incubation Treatment | Percent Bropirimine Oxidase Activity Remaining, Compared With Control | |||
|---|---|---|---|---|
| Enzyme | Inhibitor (μM) | Dihydrodiol | p-Hydroxy | m-Hydroxy |
| CYP1A2 | α-Naphthoflavone (100 μM) | 3.8 | 1 | 1.4 |
| CYP2A6 | Coumarin (200 μM) | 90 | 89 | 95 |
| CYP2C9 | Sulfaphenazole (9 μM) | 91 | 97 | 94 |
| CYP2C19 | (S)-Mephenytoin (200 μM) | 94 | 94 | 88 |
| CYP2D6 | Quinidine (5 μM) | 100 | 91 | 96 |
| CYP2E1 | p-Nitrophenol (100 μM) | 89 | 93 | 95 |
| CYP3A4 | Ketoconazole (5 μM) | 90 | 90 | 92 |
| mEH | Cyclohexene oxide (1000 μM) | 62 | 124 | 110 |
| N-Actyl-cysteine (1000 μM) | 96 | 100 | 102 | |
| l-Cysteine (1000 μM) | 94 | 91 | 101 | |
Pooled human liver microsomes were incubated in the presence or absence of various chemicals, as described under “Materials and Methods.” The rates are expressed as a percentage of control (minus inhibitor) activity. The chemicals are listed according to which P450 enzyme they inhibit. Results are shown as the means of duplicate determinations.