Key takeaways:
~ The CYP2C9 gene encodes an enzyme that breaks down certain medications as well as key substances in the body, such as serotonin and arachidonic acid.
~ Variants in CYP2C9 can affect the way prescription drugs work for you.
~ CYP2C9 is also involved in the metabolism of THC from cannabis.
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CYP2C9: Breaking down prescription medications and more
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or slow a medication, toxicant, or supplement is broken down and eliminated by your body.
The CYP2C9 gene is part of the CYP450 family of enzymes needed for phase I detoxification of toxicants and medications. Read more about phase I and phase II detoxification.
The CYP2C9 gene codes for an enzyme found mainly in the liver that metabolizes (breaks down) quite a few medications as well as natural substances in the body.
Medications metabolized by CYP2C9:
Some commonly prescribed medications that are metabolized by the CYP2C9 enzyme include:
- losartan (blood pressure)
- warfarin (anticoagulant)
- acenocoumarol (anticoagulant)
- tolbutamide (diabetes)
- glipizide (diabetes)
- ibuprofen (NSAID, pain relief)
- celecoxib (NSAID, pain relief)
- montelukast (asthma)
- naproxen (NSAID, pain relief)
A complete list can be found on Pharmacy Times.
There are several genetic variants of CYP2C9 that either increase or decrease the activity level of the enzyme. This is important when looking at how your body will respond to different doses of common drugs.
Let’s look at some examples of how the CYP2C9 genetic variants are important:
- With some loss-of-function CYP2C9 variants, NSAIDs such as ibuprofen and celecoxib are not broken down as fast. Taking additional doses can then overload the body with too much of the medication, causing an increased risk of gastrointestinal bleeding.[ref]
- Celecoxib, commonly prescribed for arthritis or joint pain, is metabolized by the CYP2C9 enzyme. A new study recommends a lower starting dosage for those with reduced enzyme function.[ref]
- Warfarin is an anticoagulant often prescribed after strokes or for those at risk for blood clots. Dosages vary widely and are determined by genetic factors based on CYP2C9 and VKORC1 variants.
- A commonly prescribed statin, rosuvastatin, is also partially metabolized by CYP2C9. A recent study found that those with slow CYP2C9 variants had more of a reduction in LDL levels when using rosuvastatin.[ref]
- THC, the active component of cannabis, is partially metabolized by CYP2C9.[ref]
Inhibitors of CYP2C9:
Fluvoxamine and fluoxetine, which are SSRIs, inhibit CYP2C9 function. This can be a problem when taken along with medications that are metabolized using CYP2C9, such as Warfarin. People using fluvoxamine and fluoxetine along with Warfarin are at a 3-fold risk of having altered clotting times (INR).[ref]
Your doctor and pharmacist should be able to give you more information on CYP2C9 inhibitor interactions.
Endogenous substances metabolized by CYP2C9:
The CYP enzymes aren’t just hanging around in the body waiting for a prescription medication to arrive. They also break down substances naturally formed in the body. CYP2C9 also breaks down:[ref]
- linoleic acid
- arachidonic acid
- serotonin
Natural supplements metabolized by CYP2C9:
In addition to prescription medications, CYP2C9 is involved in the metabolism of natural flavonoids that are often used as supplements.[ref]
- naringenin
- naringin
- quercetin
- rutin
St. John’s wort and Ginkgo biloba are strong inhibitors of CYP2C9.[ref]
What should you do if you are a slow or fast CYP2C9 metabolizer?
Knowing how your body metabolizes different medications and supplements is important. But it is not as simple as taking less of a medicine if you are a slow metabolizer. Many medications can be metabolized by using several different CYP enzymes, so your body may have a good backup route for breaking down some drugs and toxins. For example, the prescription sleep medication zolpidem is metabolized through several different CYP enzymes, including CYP2C9. However, research shows the slow CYP2C9 enzymes only matter for zolpidem in people who also have slowed CYP3A4 enzyme function.[ref]
Some medications need to be metabolized using a CYP enzyme before they will begin to work because the metabolite is actually the drug. This type of medication is called a pro-drug since the actionable drug is formed by your body breaking down the pro-drug. For other medications, the tablet you take is the actual drug, and the speed at which it is broken down affects how long it stays in your system.
This gets complicated (talk with your doctor):
Knowing whether you are a slow or fast metabolizer is only part of the picture. You also need to understand how the drug works and whether there are any interactions with other medications. This is one of those ‘talk with your doctor and pharmacist’ situations — especially if you are taking several prescription medications.
Children aren’t just small adults:
To add one more layer of complexity here, most studies on drug metabolism use adult study participants. In children, some medications metabolize slightly differently. For example, valproate, an epilepsy medication, mainly uses CYP2C9 in children for metabolization but not in adults.[ref]
CYP2C9 Genotype Report:
Lifehacks:
Talk with your doctor or pharmacist if you have questions about specific prescription medications.
Short-term fasting may reduce CYP2C9 activity; a 36-hour fast reduced CYP2C9 activity by 19%. Keep this in mind if you are taking a medication metabolized by CYP2C9. This can affect how long the medication is active for you. For example, this could affect your clotting time if you take warfarin while fasting.[ref]
Check CYP2C8 variants also:
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CYP2D6: Medication Interactions, Natural Inhibitors, and Anxiety Traits
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