Effect of human P450 inhibitors or human FMO3 inhibitor on highly purified enzyme-mediated metabolism of oxycodone N-oxide
Values are expressed as means ± S.D., mean of four determinations, pH 7.4. Oxycodone N-oxide was present at 20 µM. Incubations were conducted for 10 min.
| Description | Oxycodone | Oxycodone N-Oxide | Noroxycodone | Oxymorphone | Noroxymorphone |
|---|---|---|---|---|---|
| None | 0.004 ± 0.001 | 14.6 ± 0.8 | ND | ND | ND |
| Control | 0.01 ± 0.002 | 15.3 ± 1.0 | ND | ND | ND |
| CYP1A1 | 0.06 ± 0.003 | 14.3 ± 0.2 | ND | ND | ND |
| CYP1A1 + α-Naphthoflavone | 0.04 ± 0.02 | 14.3 ± 0.2 | ND | ND | ND |
| CYP2A6 | 0.02 ± 0.001 | 1.94 ± 0.1 | ND | ND | ND |
| CYP2A6+Tranylcypromine | 0.13 ± 0.001 | 1.9 ± 0.1 | ND | ND | ND |
| CYP3A4 | 0.06 ± 0.01 | 1.8 ± 0.1 | ND | ND | ND |
| CYP3A4+TAO | 0.06 | 1.9 ± 0.1 | ND | ND | ND |
| CYP2D6 | 0.04 ± 0.002 | 14.2 ± 0.5 | ND | ND | ND |
| CYP2D6+Quinidine | 0.02 ± 0.001 | 13.6 ± 0.8 | ND | ND | ND |
| FMO3a | 0.002 ± 0.0002 | 4.4 ± 0.2 | ND | ND | ND |
| FMO3a+MMI | 0.002 ± 0.0 | 4.0 ± 0.2 | ND | ND | ND |
MMI, methyl mercapto imidazore, an alternal substrate competitive inhibitor of FMO3; ND, not detected; TAO, troleandomycin.
↵a Values were expressed as the mean ± S.D. as (nM/min)/84.5 µg of FMO3, mean of four determinations, pH 7.4.