Editing CYP2D6 (section)

== Genotype/phenotype variability ==

CYP2D6 shows the largest [[phenotype|phenotypical]] variability among the CYPs, largely due to [[genetics|genetic]] [[polymorphism (biology)|polymorphism]]. The [[genotype]] accounts for normal, reduced, and non-existent CYP2D6 function in subjects. Pharmacogenomic tests are now available to identify patients with variations in the CYP2D6 allele and have been shown to have widespread use in clinical practice.<ref name="PMID24413808" />
The CYP2D6 function in any particular subject may be described as one of the following:<ref name="pmid11851634">{{cite journal | vauthors = Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A | title = Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs | journal = British Journal of Clinical Pharmacology | volume = 53 | issue = 2 | pages = 111–122 | date = February 2002 | pmid = 11851634 | pmc = 1874287 | doi = 10.1046/j.0306-5251.2001.01548.x }}</ref>
* poor metabolizer – little or no CYP2D6 function
* intermediate metabolizers – metabolize drugs at a rate somewhere between the poor and extensive metabolizers
* extensive metabolizer – normal CYP2D6 function
* ultrarapid metabolizer – multiple copies of the ''CYP2D6'' gene are expressed, so greater-than-normal CYP2D6 function occurs

A patient's CYP2D6 phenotype is often clinically determined via the administration of [[debrisoquine]] (a selective CYP2D6 substrate) and subsequent plasma concentration assay of the debrisoquine [[metabolite]] (4-hydroxydebrisoquine).<ref name="pmid19102711">{{cite journal | vauthors = Llerena A, Dorado P, Peñas-Lledó EM | title = Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity | journal = Pharmacogenomics | volume = 10 | issue = 1 | pages = 17–28 | date = January 2009 | pmid = 19102711 | doi = 10.2217/14622416.10.1.17 }}</ref>

The type of CYP2D6 function of an individual may influence the person's response to different doses of drugs that CYP2D6 metabolizes. The nature of the effect on the drug response depends not only on the type of CYP2D6 function, but also on the extent to which processing of the drug by CYP2D6 results in a chemical that has an effect that is similar, stronger, or weaker than the original drug, or no effect at all. For example, if CYP2D6 converts a drug that has a strong effect into a substance that has a weaker effect, then poor metabolizers (weak CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects; conversely, if CYP2D6 converts a different drug into a substance that has a greater effect than its parent chemical, then ultrarapid metabolizers (strong CYP2D6 function) will have an exaggerated response to the drug and stronger side-effects.<ref name="pmid17708140">{{cite journal | vauthors = Lynch T, Price A | title = The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects | journal = American Family Physician | volume = 76 | issue = 3 | pages = 391–396 | date = August 2007 | pmid = 17708140 }}</ref> Information about how human genetic variation of CYP2D6 affects response to medications can be found in databases such PharmGKB,<ref>{{cite web |title=PharmGKB |url=https://www.pharmgkb.org/gene/PA128/prescribingInfo |access-date=3 October 2022 |website=PharmGKB |language=en |archive-date=3 October 2022 |archive-url=https://web.archive.org/web/20221003090823/https://www.pharmgkb.org/gene/PA128/prescribingInfo |url-status=live }}</ref> Clinical Pharmacogenetics Implementation Consortium (CPIC).<ref>{{cite web |title=CYP2D6 CPIC guidelines |url=https://cpicpgx.org/gene/cyp2d6/ |access-date=3 October 2022 |website=cpicpgx.org |language=en-US |archive-date=3 October 2022 |archive-url=https://web.archive.org/web/20221003084825/https://cpicpgx.org/gene/cyp2d6/ |url-status=live }}</ref>