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Inducible?

I have heard that CYP2D6 is a non-inducible enzyme in human hepatocytes. This article states otherwise. Does anyone have any specific references that may indicate one way or the other?

I've seen some speculation about that too, but here are a few references: PMID 15001973, PMID 12354285 -Techelf 11:55, 12 May 2005 (UTC)

There are no confirmed 2D6 inducers although rifampin may be. —Preceding unsigned comment added by Genelex (talk • contribs) 17:38, 4 June 2009 (UTC)

Hyperforin (St. John's Wort) was listed as an inducer, although it is an inhibitor. I moved it accordingly, with a reference. Fridgebuzz (talk) 19:22, 12 February 2011 (UTC)

rifampin and dexamethasone per indiana university, though this is newer information and just a couple years ago there were none (to my knowledge)

More recent References: "...although induction by any drug has not been observed thus far. CYP2D6 was also one of the first enzymes for which a highly polymorphic expression could be shown leading to a widespread range of functionality, from a complete lack of a functional enzyme to overexpression due to multiplication of active alleles Ref: Recent examples on the clinical relevance of the CYP2D6 polymorphism and endogenous functionality of CYP2D6." Ref: Drug Metabolism and Drug Interactions. Volume 28, Issue 4, Pages 209–216. Haertter S, Dept Translational Medicine, Clinical PK/PD, Boehringer Ingelheim Pharmaceuticals, Inc. ISSN (Online) 2191-0162, ISSN (Print) 0792-5077, DOI: 10.1515/dmdi-2013-0032, October 2013

"CYP2D6 is largely uninducible by prototypical CYP inducers such as phenobarbital, rifampin and dexamethasone..." Ref:Curr Med Chem. 2009;16(21):2661-805. Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development. Zhou SF, Liu JP, Lai XS. — Preceding unsigned comment added by 134.173.101.159 (talk) 18:01, 24 September 2015 (UTC)

Tamoxifen

This article seems a bit in need of updating to me! I'm just learning about this stuff, but according to the Genelex website at www.healthanddna.com, there are FOUR types of CYP2D6 metabolizers, not three - the intermediate metabolizer is missing from this article. In addition, the substrate table is out of date, as it no longer accurately reflects the Flockhart table - for example, on the Flockhart table buproprion is now listed as a strong inhibitor. Furthermore, CYP2D6 is very important to the metabolism of tamoxifen and that story deserves a paragraph in it's own right.

However, I'm not a genetecist, just someone who had breast cancer who has been tested for the CYP2D6 metabolism, found to be an intermediate metabolizer, and who is trying to figure out what that means for taking tamoxifen, as there's no sense in taking something I can't metabolize. There are some leads on my cancer blog, www.imaginebrightfutures.wordpress.com, but other than that, I'm still not at the place where I feel comfortable writing this stuff up, I just wanted to note that it needs to be done! To all who contributed to this article so far, it's a great start! —Preceding unsigned comment added by Aunt Amanda (talk • contribs) 04:06, 5 January 2008 (UTC)

If you look carefully, the article defines an extensive metaboliser as one who has normal or reduced activity. If you're an intermediate metaboliser, I would assume you can metabolize tamoxifen fine. Since tamoxifen is a prodrug and must undergo metabolism before being active, it would be beneficial for a patient taking tamoxifen to be able to metabolize it more readily. A patient taking tamoxifen should avoid taking medications, such as SSRI's, which compete with tamoxifen for CYP2D6 or medications which inhibit CYP2D6 activity. It might also be a good idea for low metabolizers taking tamoxifen to try to induce CYP2D6 activity. With that said, I'm a chemist and not an MD, so don't take my word as medical advice. This isozyme is of particular interest to me. I'll attempt to incorporate your suggestions in any updates I make to the article, however, I think a lot of your questions are answered in the article on tamoxifen. --Jmcclare (talk) 03:44, 10 April 2008 (UTC)

Here is some tamoxifen specific dosing information that may help. Remember that over the counters and herbals can also inhibit 2D6.

The information below can help you understand and apply the results of the Tamoxifen DNA Prescription Drug Reaction Test currently offered by Genelex.

Testing for CYP2D6 places individuals in one of four categories:

• Extensive Metabolizers (EM) represent the norm for metabolic capacity. Genotypes consistent with the EM phenotype include two active forms of the gene producing the drug metabolizing enzyme and therefore posses the full complement of drug metabolizing capacity. Generally, extensive metabolizers can be administered drugs which are substrates of the enzyme following standard dosing practices. • Intermediate Metabolizers (IM) may require higher than average tamoxifen dosages for optimal therapeutic response. In addition, multiple drug therapy should be monitored closely. Genotypes consistent with the IM phenotype are those with only one active form of the gene producing the drug metabolizing enzyme and therefore have reduced metabolic capacity. • Poor Metabolizers (PM) are at high risk of therapeutic failure because the have a compromised ability to generate the active form of tamoxifen. Genotypes consistent with the PM phenotype are those with no active genes producing the drug metabolizing enzyme. These individuals have a deficiency in drug metabolism. • Ultra-extensive Metabolizers (UM) may require a decreased dosage due to higher than normal rates of tamoxifen conversion to endoxifen. Genotypes consistent with UM phenotype include three or more active genes producing the drug metabolizing enzyme and therefore have increased metabolic capacity.

Therapy Modification

Phenotype prevalence is 10 % PM, 7% UM, and 35% IM. PM – Consider an alternative medication IM – Consider an increased dose and avoid multiple drug therapy that inhibits 2D6. UM- Consider a reduced dose and avoid multiple drug therapy that inhibits 2D6. EM – Follow standard dosing practices. Avoid multiple drug therapy that inhibits 2D6.

Inhibitors of Cytochrome P-450 2D6 Inhibitors refer to drugs that reduce the ability of the pathway to process drugs. Co-administration will decrease conversion of tamoxifen to the active metabolite endoxifen increasing the possibility of treatment failure. Genelex includes 90-days access to GeneMedRx drug and gene interaction software with each test so healthcare providers can see if any co-administered medications are inhibiting CYP2D6. You can see a demo and try it free at www.GeneMedRx.com/demo

Here is an abridged list of inhibitors. amiodarone chlorpromazine doxorubicin methadone nevirapine ranitidine ticlopidine azelastine cimetidine haloperidol metoclopramide nicardipine ritonavir trifluperidol celecoxib cisapride indinavir moclobemide paroxetine saquinavir chlorpheniramine cocaine levomepromazine nelfinavir quinidine terfenadine

I am a molecular biologist by training and work at Genelex - Kristine —Preceding unsigned comment added by Genelex (talk • contribs) 17:34, 4 June 2009 (UTC)

Atenolol

I added atenolol as a 2D6 substrate; see <http://www.drugbank.ca/cgi-bin/getCard.cgi?CARD=APRD00172>.

Gibberish

I am highly thankfull that there are people that smart to understand the full context of the text written down which is meant as an explenation. But even with my higher education and to my opinion fairly proper knowledge of medication i have a real hard time understanding what the first 15 lines of text are all about, let alone the rest of it. Is there anyone out there who can explain it in language a 12 year old would understand? Perhaps, i could also get a grasp of what is meant here then too. I was sent here due to a little in depth information about a drug related to influencing a part of autism. Thanks a lot! Pim 83.81.164.24 (talk) 21:30, 2 October 2010 (UTC)

• I second everything said here. The whole of the article is virtually incomprehensible. For example, substrates are a major part of the chart provided, yet there is virtually no mention of what a substrate is in the explanatory text. I hold a doctorate degree from the University of California and I cannot discern from this article the principal question which anyone looking up CYP2D6 will have: which drugs are affected by CYP2D6 and in what way are they affected by it. QuintBy (talk) 18:51, 28 November 2012 (UTC)

• I have extensively rewritten the lead to provide more clarity and background information. Hopefully the consequences if a drug is a CYP2D6 substrate, inhibitor, or an inducer is now clearer. I note that risperidone which is used to treat autism is a CYP2D6 substrate. Hence the risperidone dose may have to be adjusted up or down depending on whether the patient is a slow or fast CYP2D6 metabolizer respectively. Of course, please feel free to make further edits. Boghog (talk) 14:13, 10 August 2013 (UTC)

Suspicious Edit

Revisions by NEMESIS91 on this article look suspicious (the line "Shawn Makuyana expressed the metbolism as a function of drug power {http//:www.uz.ac.zw/biochem{{</ref>pmid=236609}}.", especially when the ref link appears to be broken, and the other wiki page this user has made is for the cited person Shawn Makuyana (which has been nominated for deletion on the grounds of it being about themselves). I would remove the edits here myself, but have no knowledge of this subject so I thought it best to leave it up to those who do. Bananastalktome (talk) 04:19, 11 May 2012 (UTC)

Be bold if you see something fishy. -- Richiez (talk) 10:53, 11 May 2012 (UTC)

Is CYP2D6 same ase CYPD2D6? That should be mentioned in the article. 2D6 vs D2D6.

91.155.24.127 (talk) 10:53, 20 April 2017 (UTC)

I am assuming CYP2D6 is real, and CYPD2D6 is a fairly common synonym derived from a widely-disseminated misspelling.

A. WP redirects D2D6 to 2D6.

B. Google has "About 1,260,000 results" for 2D6.

C. Google has "About 1,680 results" for D2D6.

D. I went through 5 pages of Google results, and came away seeing 2D6 as having been so widely corrupted that scientists see the two versions as identical, even at the level of scientific articles.

It's like "same difference", "could care less" and "nucular".

You could be bold, with a footnote explaining the evidence for their being the same CYP enzyme. --Quisqualis (talk) 00:51, 21 April 2017 (UTC)

Neither UniProt nor HUGO list CYPD2D6 as a synonym of CYP2D6. Hence I think you are right that CYPD2D6 is a (surprisingly common) misspelling. However I am not sure we need to mention this, unless you can find a source that Boghog (talk) 03:19, 21 April 2017 (UTC)

Anandamide

The endogenous cannabinoid anandamide is a substrate for CYP2D6. Source: https://www.ncbi.nlm.nih.gov/pubmed/18698000 Tkadm30 (talk) 15:45, 28 April 2017 (UTC)

Contradictory information on the strength of Fluvoxamine's inhibition of CYP2D6

Hi there, this page cites this link for Fluvoxamine being a weak CYP2D6 inhibitor meanwhile the page for Fluvoxamine cites this paper (Full text available via scihub.) stating it's a moderate CYP2D6 inhibitor.

Could someone assist in ironing out this discrepancy? 203.54.35.151 (talk) 12:02, 25 December 2020 (UTC)

Oxidoreductase

In the info box under molecular function, “oxidoreductase activity” is entered three times with different levels of additional information. That seems like it was probably an accident. I suggest that someone who understands this article take a look and fix it. Isomorphic (talk) 12:10, 10 June 2021 (UTC)

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