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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)

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 In addition, the substrate table is out of date, as it no longer accurately reflects the Flockhart table - for example, on the Flockhart table buproprion is now listed as a strong inhibitor.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)

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)