Table 1.
Change in oxycodone:oxymorphone ratio depending on patient genotype or use of CYP450-inhibitor drugs.
| CYP2D6 Activity | Oxycodone/Oxymorphone Concentration Ratio in Plasma | Oxycodone/Oxymorphone Free-Drug Concentration Ratio in Plasma | Oxycodone/Oxymorphone Free-Drug Concentration Ratio in the Brain * | Oxycodone/Oxymorphone Relative Contribution to μ-Opioid Receptor-Binding Considering the Free-Drug Concentration Ratio in the Brain ** |
|---|---|---|---|---|
| UM CYP2D6 | 32:1 | 19:1 | 57:1 | 0.6:1 |
| NM CYP2D6 | 43:1 | 26:1 | 78:1 | 0.8:1 |
| PM CYP2D6 | 300:1 | 180:1 | 540:1 | 5.4:1 |
| With potent CYP2D6 inhibitors | 110:1 | 66:1 | 198:1 | 2:1 |
| With potent CYP3A4 inhibitors | 56:1 to 21:1 | 34:1 to 13:1 | 102:1 to 39:1 | 1:1 to 0.4:1 |
CYP2D6: cytochrome P450 2D6; UM: ultra-rapid metabolizer; NM: normal metabolizer; PM: poor metabolizer; CYP3A4: cytochrome P450 3A4; *: assuming a conservative brain-to-blood unbound concentration ratio of 3.0 for oxycodone and of 1.0 for oxymorphone; **: assuming a conservative brain-to-blood unbound concentration ratio of 3.0 for oxycodone and of 1.0 for oxymorphone and a potency ratio of 1:100 for oxycodone vs. oxymorphone.