Cytochrome P450 2D6
CYP2D6
"Too Darn Sexy"
2D6 metabolizes ~ 12% of prescription drugs. Notice how all the -oxetines are 2D6 inhibitors and/or substrates.
5% of individuals are 2D6 ultrarapid metabolizers (UM). 10% are poor metabolizers (PM).
Conclusion: 2D6 interactions need to be understood by prescribers of antidepressants and antipsychotics. To avoid 2D6 interactions, use Lexapro or Zoloft instead of Prozac/Paxil. Consider Invega ($330) instead of Risperdal ($12), although cost is an issue.
Among the CYP genetic assays, 2D6 is the most useful. The test is about $200 as a standalone, and is recommended prior to starting Trilafon, Mellaril, or Orap—three antipsychotics that psychiatrists rarely prescribe. For the other 2D6 substrates, serum drug levels may be more useful than genotyping. The author checks blood levels of haloperidol, risperidone and aripiprazole when there are issues with efficacy or tolerability.
2D6 poor metabolizers
2D6 poor metabolizers have defective 2D6 enzymes. Substrates are cleared slowly (by other pathways) or are unmetabolized leading to Higher blood levels, as if the patient were taking an inHibitor.
2D6 ultrarapid metabolizers
2D6 ultrarapid metabolizers clear 2D6 substrates quickly. These individuals are more likely to be non-responders to 2D6 substrates (excluding 2D6 prodrugs, which may be too strong). This genotype is relatively common among those with Middle Eastern or North African heritage.
2D6 extensive metabolizers
The “normal” phenotype. 2D6 extensive metabolizers have the typical genotype and process 2D6 substrates as expected
2D6 prodrugs
Prodrugs are substrates that are less potent than their metabolites. Ordinary substrates (beach balls) are deactivated by 2D6. Prodrugs (bowling balls) are activated by 2D6. In the presence of an inhibitor prodrugs are less effective.
2D6 inhibitors
2D6 substrates
