CYP2C19 – Metabolizing medications

The CYP2C19 enzyme is responsible for the breakdown of several popular drugs including proton pump inhibitors (Prilosec, Nexium, Prevacid), certain anti-epileptics, and an antiplatelet drug (Plavix).  CYP2C19 is also involved in activating and breaking down some hormones such as progesterone.

There are variants of the CYP2C19 gene that cause some people to be poor metabolizers and others to be fast metabolizers. You can have increased side effects (depending on the medication) either from being a slow metabolizer or a fast metabolizer.   For example, a fast metabolizer taking omeprazole to treat h. pylori may have an insufficient response due to the drug not remaining active in the body long enough.[ref]  Alternatively, some drugs such as Plavix are converted into their active drug state through CYP2C19, and being a poor metabolizer could mean that Plavix (an anticoagulant) isn’t activated quickly enough. [ref]

Valium (diazepam) is another common drug metabolized in part by CYP2C19 (along with CYP3A4). Currently, there are no official recommendations to physicians as to reducing the dosages for poor metabolizers, but there is a box warning about CYP2C19. [ref]

A couple of SSRI’s, Celexa (citalopram), Zoloft (sertraline) and Lexapro (escitalopram), are also metabolized mainly through CYP2C19.[ref]

Approximately 10 – 20% of Asians are poor metabolizers, as are 2 – 5% of people of Caucasian descent.  Up to 20-30% of Caucasians are fast metabolizers, but less than 5% of Asians are.  So there is a wide variation on how drugs are metabolized by this gene.

Here is a complete list of drugs metabolized by CYP2C19.

Beyond Drug Metabolism:
So for a person not on any drugs, what does the CYP2C19 gene do?  Obviously, we don’t have a gene just waiting around for us to take a valium.  It is involved (minor) in metabolizing melatonin[ref] and is also involved in the metabolism of estradiol.[ref]


Poor metabolizers:  

Check your 23andMe results for rs4244285 (v4, v5):

  •  AA:  non-functioning (CYP2C19*2)
  •  AG: poorer metabolizer
  •  GG:  Normal    [ref]

 

Check your 23andMe results for rs4986893 (v4, v5):

  •  AA: poor metabolizer (CYP2C19*3), increased risk of lung cancer[ref]
  •  AG: slow metabolizer
  •  GG:  Normal    [ref]

Ultra-fast metabolizers:

Check your 23andMe results for rs12248560 (v4, v5):

  •  CC: normal
  •  CT: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment
  •  TT: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment [ref]

 


Lifehacks:

Don’t smoke:  If you are a CYP2C19 poor metabolizer and a smoker, you are at a 5x increased risk of lung cancer[ref] and a 17x increased risk of laryngeal cancer.[ref]

Interactions with natural substances:

  • D-limonene, a component of citrus essential oils, is also metabolized through CYP2C19.  If you are a poor metabolizer and taking a medication metabolized through CYP2C19, you may not want to take supplements or essential oils with d-limonene at the same time as the medication.
  • Inhibitors of CYP2C19 may also interfere with medications that you are taking.  Common supplements such as quercetin, berberine, and caffeic acid.[ref][ref]
  • Inducers of CYP2C19 include low-dose aspirin.[ref]

Read more: This is part of an ongoing series of posts about the CYP450 enzymes and detoxification.

 

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