The Metabolism of Opioids: Factors That Impact Metabolism

Opioids are mostly metabolized in the liver, with most undergoing CYP-mediated oxidation. The metabolization process continues until the opioids have been altered enough that they can be excreted from the body through a person’s urine. 

Some people may have health conditions or be taking certain drugs that can affect this process, making a standard dose of opioids stronger or weaker than would typically be expected. 

How Are Opioids Metabolized?

Opioids, just like most drugs, undergo metabolization in the liver in two phases. [1]:

• Phase 1 metabolism happens first and breaks the drug down into its active metabolites, or the metabolites that then go on to have effects in the body
• Phase 2 metabolism involves the metabolites being broken down once they have exerted their effect in the body so they can be excreted either through the feces or the urine. 

What Factors Influence Metabolism?

Factors that can influence a person’s metabolism include genetics, certain health disorders, and drug interactions.[2] 

First, some people metabolize certain drugs more slowly or more quickly. This is thought to be due mostly to genetics. At this time we don’t have a good way of predicting which individuals will be “fast’ or “slow” metabolizers of opioids. [3]

Second, certain medical conditions may cause a person to metabolize opioids more slowly. Patients with Chronic liver disorders in particular have livers that do not process metabolites as well as their healthy counterparts. This may mean they need lower doses of certain medications, including opioids. 

Lastly, certain drugs may inhibit or activate the cytochrome P450 system of the liver, which is the most common system the liver uses to metabolize drugs like opioids. This means that certain medications may cause opioids to be metabolized more quickly or more slowly. 

Are All Opioids Metabolized the Same Way?

While not all opioids are metabolized in exactly the same way, they do broadly share many similarities. Virtually all short-acting opioids, such as morphine and hydrocodone, metabolize such that they’re only detectable in urine for between one to three days.[4] Long-acting opioids, like methadone, take longer to metabolize, Methadone is detectable in urine for about three to seven days.

Why Is Understanding Metabolism Important?

Fundamentally, metabolism is what determines how a given dose of a drug is going to affect the body. It’s critical for doctors to understand metabolism, as not all patients will react in the standard way to a dose of opioids if they have certain health or genetic conditions or are taking certain types of other medications.[5] This is why it’s important to be direct and honest with a medical professional who is considering prescribing opioids, so they know the correct type and dose of opioid that will work best for you. 

This also highlights one of many reasons why misusing opioids can be so dangerous. Differences in individual metabolism can lead to opioids having weaker or stronger effects, particularly if combined with other medications. [6] This can lead to risks of opioid overdose in patients who are metabolizing opioids more slowly. 

Always use opioids with caution, and reach out to your doctor if you are taking other medications or have any health conditions that might affect your metabolism of opioids.