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CYP2B6 is a detox enzyme that processes drugs such as efavirenz, bupropion, cyclophosphamide, and thiotepa. The CYP2B6 gene is highly variable, and people with different variants have different enzyme activity. That explains why these drugs have different effects on different people. Read on to find out more about this enzyme, gene variants, and factors that increase or decrease its activity.
What is CYP2B6?
CYP2B6 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).
This enzyme metabolizes:
- Nicotine. A small part of nicotine’s metabolism (~10%) occurs via CYP2B6 (R).
- Drugs such as ketamine (R), efavirenz (R), bupropion, cyclophosphamide (R, R), thiotepa (R), methadone (R), and MDMA (ecstasy) (R).
CYP2B6 Gene Polymorphism
With over 100 described SNPs, CYP2B6 is one of the most variable CYP genes in humans (R).
rs3745274 (T) is the most common and clinically significant variant. It results in markedly reduced enzyme activity (R).
It is significant because it occurs commonly (particularly in Africans, Asians, and Hispanics) and influences important drugs that are processed by CYP2B6 (e.g. efavirenz, bupropion, cyclophosphamide) (R).
This variant was more frequent in nicotine-dependent individuals (421 subjects) (R).
The T variant is associated with a slower metabolism of efavirenz (R). This means people with this variant will have increased efavirenz exposure and nervous system-related adverse effects (821 subjects) (R).
On the other hand, CYP2B6 converts cyclophosphamide to its active form. Patients carrying at least one T are significantly less likely to achieve a complete response after chemotherapy with fludarabine plus cyclophosphamide (455 subjects) (R).
People with rs28399499 C have lower enzyme activity.
G increases enzyme activity (64 subjects) (R).
Increasing or Decreasing CYP2B6
These increase CYP2B6:
- 17β-estradiol (E2) at high concentrations (R).
These decrease CYP2B6:
- Berberine (R), found in various plants.
- Allyl isothiocyanate (R), found in mustard, radish, horseradish, and wasabi.
- Citral and geraniol (R), found in essences of flowers, plants oils, and herbal medicines.
- Clopidogrel (R).
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