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 .
This enzyme metabolizes:
- Nicotine. A small part of nicotine’s metabolism (~10%) occurs via CYP2B6 .
- Drugs such as ketamine , efavirenz , bupropion, cyclophosphamide [5, 6], thiotepa , methadone , and MDMA (ecstasy) .
CYP2B6 Gene Polymorphism
With over 100 described SNPs, CYP2B6 is one of the most variable CYP genes in humans .
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) .
This variant was more frequent in nicotine-dependent individuals (421 subjects) .
People with the T variant have a lower clearance of ketamine. This results in higher drug levels that may be associated with more frequent ketamine adverse effects (49 chronic pain patients) .
The T variant is associated with a slower metabolism of efavirenz . This means people with this variant will have increased efavirenz exposure and nervous system-related adverse effects (821 subjects) .
Similarly, this variant increases nevirapine exposure. Children with T/T had improved immunological responses to this drug (126 subjects) .
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) .
People with G in this position have a higher clearance and a lower level of (S)-methadone (366 subjects) .
People with rs28399499 C have lower enzyme activity.
Smokers with A/A had higher smoking cessation success rate on bupropion therapy (478 subjects) .
A/G women with liver-metastatic breast cancer had a 47% reduced risk of death and a 6-month-longer overall survival on docetaxel and thiotepa therapy (153 patients) .
Increasing or Decreasing CYP2B6
These increase CYP2B6:
- 17β-estradiol (E2) at high concentrations .