Which opioids are hepatically activated or inactivated?
Almost all opioids are metabolized in the liver. Some are metabolized to inactive compounds, some to active compounds, and some to both. For example, hydrocodone is metabolized to the more active hydromorphone by cytochrome 2D6 (CYP2D6) and by CYP3A4 to inactive norhydrocodone. Likewise, oxycodone is metabolized to the more potent oxymorphone by CYP2D6 and to inactive noroxycodone by CYP3A4. Codeine is basically inactive as an analgesic until CYP2D6 converts it to morphine. When providing a separate drug that enhances production of certain hepatic enzymes (inducers) or diminishes production (inhibitors), problems can arise in terms of potential opioid overdose. Depending on genetic phenotype, some patients have more or less of various hepatic isoenzymes. The only opioids that do not rely on CYP enzymes for metabolism are morphine, oxymorphone, hydromorphone, levorphanol, and tapentadol.