Estimates of Michaelis-Menten parameters for oxycodone metabolite formation in Gentest Supersomes containing recombinant CYP3A4, CYP3A5, and CYP2D6 kcat is defined as Vmax per mole of expressed enzyme. Values in parentheses represent the 95% confidence intervals of the regression estimates.
Reaction | P450 | Km | kcat | CLint |
|---|---|---|---|---|
| μM | 1/min | μl/min/pmol P450 | ||
| Oxycodone→Noroxycodone | 3A4 | 377 (235—519) | 4.7 (3.78—5.57) | 0.012 |
| 3A4 + b5 | 670 (595—744) | 21.7 (20.28—23.14) | 0.032 | |
| Oxycodone→Noroxycodonea | 3A5 | 0.017 | ||
| 3A5 + b5 | 0.040 | |||
| Oxycodoneb→Oxymorphone | 2D6*1 | 39.8 (31.0—48.7) | 11.4 (10.8—12.0) | 0.286 |
| Noroxycodone→Noroxymorphone | 2D6*1 | 20.5 (15.2—25.9) | 14.9 (14.1—15.7) | 0.727 |
↵ a CYP3A5-mediated formation of noroxycodone did not reach apparent saturation within the substrate concentration used
↵ b Two-fold difference between the oxycodone Km in HLM and Supersomes has been noted and may be attributed to variable levels of cytochrome P450 reductase (OR) present in Gentest Supersomes