one person’s 100mg morphine equivalent dose is another person’s 200mg morphine equivalent dose
In the most straightforward example, consider that a single opioid dose in a 150 pound person may not achieve the same benefit or toxicity as it would in a 300 pound person
From a scientific perspective, the amount of active drug in the blood may be more or less, depending on how the body processes or metabolizes the drug
an entire science known as pharmacogenomics has evolved that helps explain why some patient might respond better or worse to one drug (or a particular dose) compared to another drug
Different opioids undergo different metabolic pathways. Some are metabolized to more active drugs, some are metabolized to less active drugs, some are metabolized to inactive drugs, and others are metabolized to all or some of the above
There are individual enzymes in the liver known as cytochrome P450 enzymes, abbreviated CYP 450.
Select examples of liver enzyme Phase I metabolism:
- Codeine (no activity) (2D6) –> morphine (more potent and active)
- Codeine (no activity) (3A4) –> norcodeine (inactive) Hydrocodone (active)
- (2D6)–> hydromorphone (more potent and more active) Hydrocodone (active)
- (3A4) –> norhydrocodone (far less potent and less active) Oxycodone (active)
- (2D6)–> oxymorphone (more potent and more active) Oxycodone (active)
- (3A4) –> noroxycodone (inactive)
There are many more enzymes involved and various phases to opioid metabolism. In fact, the oral absorption or lack thereof is often dependent on yet another enzyme
Even more of an issue is that production or inhibition of these enzymes occurs with certain drugs. For example, the Hepatitis C drug telaprevir can enhance methadone absorption from the gastrointestinal tract and also enhance absorption into the brain. This could happen within 48 hours of taking a single dose of newly prescribed telaprevir. And we wonder why so many people die from methadone – it is not just about “overdosing” by taking too much. It is far more complex!
Although this is a very narrow and simplistic overview, it is intended to demonstrate reasons why not everybody responds to or tolerates the same drugs or the same dose.