CYP2D6

Last updated

CYP2D6
CYP2D6 structure.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases CYP2D6 , CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2, CYP2DL1, CYPIID6, P450-DB1, P450C2D, P450DB1, cytochrome P450 family 2 subfamily D member 6, Cytochrome P450 2D6
External IDs OMIM: 124030 HomoloGene: 133550 GeneCards: CYP2D6
Orthologs
SpeciesHumanMouse
Entrez

1565

n/a

Ensembl

n/a

UniProt

P10635

n/a

RefSeq (mRNA)

NM_000106
NM_001025161

n/a

RefSeq (protein)

NP_000097
NP_001020332

n/a

Location (UCSC) Chr 22: 42.13 – 42.13 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.

CYP2D6, a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, via the addition or removal of certain functional groups  – specifically, hydroxylation, demethylation, and dealkylation. [3] CYP2D6 also activates some prodrugs. This enzyme also metabolizes several endogenous substances, such as hydroxytryptamines, neurosteroids, and both m-tyramine and p-tyramine which CYP2D6 metabolizes into dopamine in the brain and liver. [3] [4]

Considerable variation exists in the efficiency and amount of CYP2D6 enzyme produced between individuals. Hence, for drugs that are metabolized by CYP2D6 (that is, are CYP2D6 substrates), certain individuals will eliminate these drugs quickly (ultrarapid metabolizers) while others slowly (poor metabolizers). If a drug is metabolized too quickly, it may decrease the drug's efficacy while if the drug is metabolized too slowly, toxicity may result. [5] So, the dose of the drug may have to be adjusted to take into account of the speed at which it is metabolized by CYP2D6. [6] Individuals who have ultrarapid polymorphism, however, may metabolize prodrugs, such as codeine or tramadol, to potentially fatal levels either through breast milk [7] [8] [9] such as treating post-cesarian section pain. These drugs may also cause serious toxicity in ultrarapid metabolizer patients when used to treat other post-operative pain, such as after tonsillectomy. [10] [11] [12] Other drugs may function as inhibitors of CYP2D6 activity or inducers of CYP2D6 enzyme expression that will lead to decreased or increased CYP2D6 activity respectively. If such a drug is taken at the same time as a second drug that is a CYP2D6 substrate, the first drug may affect the elimination rate of the second through what is known as a drug-drug interaction. [5]

Gene

The gene is located on chromosome 22q13.1. near two cytochrome P450 pseudogenes (CYP2D7P and CYP2D8P). [13] Among them, CYP2D7P originated from CYP2D6 in a stem lineage of great apes and humans, [14] the CYP2D8P originated from CYP2D6 in a stem lineage of Catarrhine and New World monkeys' stem lineage. [15] Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [16]

Genotype/phenotype variability

CYP2D6 shows the largest phenotypical variability among the CYPs, largely due to genetic 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. [17] The CYP2D6 function in any particular subject may be described as one of the following: [18]

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). [19]

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. [20] Information about how human genetic variation of CYP2D6 affects response to medications can be found in databases such PharmGKB, [21] Clinical Pharmacogenetics Implementation Consortium (CPIC). [22]

Genetic basis of variability

The variability in metabolism is due to multiple different polymorphisms of the CYP2D6 allele, located on chromosome 22. Subjects possessing certain allelic variants will show normal, decreased, or no CYP2D6 function, depending on the allele. 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. [17] The current known alleles of CYP2D6 and their clinical function can be found in databases such as PharmVar. [23]

CYP2D6 enzyme activity for selected alleles [24] [25]
AlleleCYP2D6 activity
CYP2D6*1normal
CYP2D6*2normal
CYP2D6*3none
CYP2D6*4none
CYP2D6*5none
CYP2D6*6none
CYP2D6*7none
CYP2D6*8none
CYP2D6*9decreased
CYP2D6*10decreased
CYP2D6*11none
CYP2D6*12none
CYP2D6*13none
CYP2D6*14none
CYP2D6*15none
CYP2D6*17decreased
CYP2D6*19none
CYP2D6*20none
CYP2D6*21none
CYP2D6*27normal
CYP2D6*29decreased
CYP2D6*31none
CYP2D6*33normal
CYP2D6*38none
CYP2D6*40none
CYP2D6*41decreased
CYP2D6*42none
CYP2D6*44none
CYP2D6*47none
CYP2D6*50decreased
CYP2D6*51none
CYP2D6*68none
CYP2D6*92none
CYP2D6*100none
CYP2D6*101none
CYP2D6 duplicationincreased

Ethnic factors in variability

Ethnicity is a factor in the occurrence of CYP2D6 variability. The reduction of the liver cytochrome CYP2D6 enzyme occurs approximately in 7–10% in white populations, and is lower in most other ethnic groups such as Asians and African-Americans at 2% each. A complete lack of CYP2D6 enzyme activity, wherein the individual has two copies of the polymorphisms that result in no CYP2D6 activity at all, is said to be about 1-2% of the population. [26] The occurrence of CYP2D6 ultrarapid metabolizers appears to be greater among Middle Eastern and North African populations. [27] [28]

Caucasians with European descent predominantly (around 71%) have the functional group of CYP2D6 alleles, producing extensive metabolism, while functional alleles represent only around 50% of the allele frequency in populations of Asian descent. [29]

This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles among the populations–approximately 10% of whites are intermediate metabolizers, due to decreased CYP2D6 function, because they appear to have the one (heterozygous) non-functional CYP2D6*4 allele, [24] while approximately 50% of Asians possess the decreased functioning CYP2D6*10 allele. [24]

Ligands

Following is a table of selected substrates, inducers and inhibitors of CYP2D6. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2D6 can be classified by their potency, such as:

Selected inducers, inhibitors and substrates of CYP2D6
Substrates
↑ = bioactivation by CYP2D6		InhibitorsInducers

Strong

Moderate

Weak

Unspecified potency

Strong

Unspecified potency

Dopamine biosynthesis

Related Research Articles

<span class="mw-page-title-main">Amitriptyline</span> Tricyclic antidepressant

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

<span class="mw-page-title-main">Cytochrome P450</span> Class of enzymes

Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown, steroid hormone synthesis, drug metabolism, and the biosynthesis of defensive compounds, fatty acids, and hormones. CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted. In almost all of the transformations that they catalyze, P450's affect hydroxylation.

<span class="mw-page-title-main">Pharmacogenomics</span> Study of the role of the genome in drug response

Pharmacogenomics, often abbreviated "PGx," is the study of the role of the genome in drug response. Its name reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup of a patient affects their response to drugs. It deals with the influence of acquired and inherited genetic variation on drug response, by correlating DNA mutations with pharmacokinetic, pharmacodynamic, and/or immunogenic endpoints.

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">CYP2E1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.

<span class="mw-page-title-main">Drug interaction</span> Change in the action or side effects of a drug caused

In pharmaceutical sciences, drug interactions occur when a drug's mechanism of action is affected by the concomitant administration of substances such as foods, beverages, or other drugs. A popular example of drug-food interaction is the effect of grapefruit in the metabolism of drugs.

<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18–24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.

<span class="mw-page-title-main">Perhexiline</span> Chemical compound

Perhexiline (Pexsig) is a prophylactic antianginal agent used primarily in Australia and New Zealand. Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O2 consumption and consequently increases myocardial efficiency. Its clinical use has been limited by its narrow therapeutic index and high inter- and intra-individual pharmacokinetic variability. It was outlawed in many countries due to its adverse effects on poor metabolisers (PM). The product has been reintroduced for patients who have contraindications, or have not responded to other treatments for angina.

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

<span class="mw-page-title-main">Grapefruit–drug interactions</span> Drug interactions with grapefruit juice

Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect is most studied with grapefruit and grapefruit juice, but similar effects have been observed with certain other citrus fruits.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

AmpliChip CYP450 Test is a clinical test from Roche and part of the AmpliChip series. The test aims to find the specific gene types ( genotypes) of the patient that will determine how he or she metabolizes certain medicines, and therefore guides the doctors to prescribe the medicine suited for the best effectiveness and least side effects.

<span class="mw-page-title-main">CYP2B6</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.

<span class="mw-page-title-main">CYP3A5</span> Enzyme involved in drug metabolism

Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.

Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene locus. A homologous locus is found in mice.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">Urs A. Meyer</span>

Urs Albert Meyer is a Swiss physician-scientist and clinical pharmacologist.

The Pharmacogenomics Knowledgebase (PharmGKB) is a publicly available, online knowledge base responsible for the aggregation, curation, integration and dissemination of knowledge regarding the impact of human genetic variation on drug response. It is funded by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS), and is a partner of the NIH Pharmacogenomics Research Network (PGRN). It has been managed at Stanford University since its inception in 2000.

Pharmacogene Variation Consortium is an international group of experts that maintains a systematic nomenclature system for allelic variations of genes that affect the metabolism of drugs.

References

  1. 1 2 3 ENSG00000275211, ENSG00000280905, ENSG00000282966, ENSG00000283284, ENSG00000272532 GRCh38: Ensembl release 89: ENSG00000100197, ENSG00000275211, ENSG00000280905, ENSG00000282966, ENSG00000283284, ENSG00000272532 – Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 Wang B, Yang LP, Zhang XZ, Huang SQ, Bartlam M, Zhou SF (2009). "New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme". Drug Metabolism Reviews. 41 (4): 573–643. doi:10.1080/03602530903118729. PMID   19645588. S2CID   41857580.
  4. ↑ Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID   24374199.
  5. 1 2 Teh LK, Bertilsson L (2012). "Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance". Drug Metabolism and Pharmacokinetics. 27 (1): 55–67. doi:10.2133/dmpk.DMPK-11-RV-121. PMID   22185816.
  6. ↑ Walko CM, McLeod H (April 2012). "Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment". Pharmacogenomics. 13 (6): 691–697. doi:10.2217/pgs.12.27. PMID   22515611.
  7. ↑ Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, et al. (2012). Tramadol Therapy and CYP2D6 Genotype. PMID   28520365.
  8. ↑ Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, et al. (2012). Codeine Therapy and CYP2D6 Genotype. PMID   28520350.
  9. ↑ Zipursky J, Juurlink DN (November 2020). "The Implausibility of Neonatal Opioid Toxicity from Breastfeeding". Clinical Pharmacology and Therapeutics. 108 (5): 964–970. doi:10.1002/cpt.1882. PMID   32378749. S2CID   218535295.
  10. ↑ Sadhasivam S, Myer CM (July 2012). "Preventing opioid-related deaths in children undergoing surgery". Pain Medicine. 13 (7): 982–3, author reply 984. doi: 10.1111/j.1526-4637.2012.01419.x . PMID   22694279.
  11. ↑ Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. (May 2012). "More codeine fatalities after tonsillectomy in North American children" (PDF). Pediatrics. 129 (5): e1343–e1347. doi:10.1542/peds.2011-2538. PMID   22492761. S2CID   14167063. Archived (PDF) from the original on 2 February 2024. Retrieved 2 February 2024.
  12. ↑ Prows CA, Zhang X, Huth MM, Zhang K, Saldaña SN, Daraiseh NM, et al. (May 2014). "Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study". The Laryngoscope. 124 (5): 1242–1250. doi:10.1002/lary.24455. PMID   24122716. S2CID   5326129.
  13. ↑ Ahmad HI, Afzal G, Jamal A, Kiran S, Khan MA, Mehmood K, et al. (2021). "In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family". BioMed Research International. 2021: 5574789. doi: 10.1155/2021/5574789 . PMC   8128545 . PMID   34046497.
  14. ↑ Wang H, Tompkins LM (September 2008). "CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme". Current Drug Metabolism. 9 (7): 598–610. doi:10.2174/138920008785821710. PMC   2605793 . PMID   18781911.
  15. ↑ Yasukochi Y, Satta Y (2011). "Evolution of the CYP2D gene cluster in humans and four non-human primates". Genes & Genetic Systems. 86 (2): 109–116. doi: 10.1266/ggs.86.109 . PMID   21670550.
  16. ↑ "Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6". Archived from the original on 8 March 2010. Retrieved 3 November 2017.
  17. 1 2 Dinama O, Warren AM, Kulkarni J (August 2014). "The role of pharmacogenomic testing in psychiatry: Real world examples". The Australian and New Zealand Journal of Psychiatry. 48 (8): 778. doi:10.1177/0004867413520050. PMID   24413808. S2CID   206399446.
  18. ↑ Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A (February 2002). "Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs". British Journal of Clinical Pharmacology. 53 (2): 111–122. doi:10.1046/j.0306-5251.2001.01548.x. PMC   1874287 . PMID   11851634.
  19. ↑ Llerena A, Dorado P, Peñas-Lledó EM (January 2009). "Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity". Pharmacogenomics. 10 (1): 17–28. doi:10.2217/14622416.10.1.17. PMID   19102711.
  20. ↑ Lynch T, Price A (August 2007). "The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects". American Family Physician. 76 (3): 391–396. PMID   17708140.
  21. ↑ "PharmGKB". PharmGKB. Archived from the original on 3 October 2022. Retrieved 3 October 2022.
  22. ↑ "CYP2D6 CPIC guidelines". cpicpgx.org. Archived from the original on 3 October 2022. Retrieved 3 October 2022.
  23. ↑ "PharmVar". www.pharmvar.org. Archived from the original on 19 May 2020. Retrieved 15 February 2024.
  24. 1 2 3 Droll K, Bruce-Mensah K, Otton SV, Gaedigk A, Sellers EM, Tyndale RF (August 1998). "Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians". Pharmacogenetics. 8 (4): 325–333. doi:10.1097/00008571-199808000-00006. PMID   9731719.
  25. ↑ "PharmVar". Archived from the original on 19 May 2020. Retrieved 20 May 2020.
  26. ↑ Lilley LL, Harrington S, Snyder JS, Swart B (2007). Pharmacology and the Nursing Process. Toronto: Mosby Elsevier. p. 25. ISBN   9780779699711.
  27. ↑ McLellan RA, Oscarson M, Seidegård J, Evans DA, Ingelman-Sundberg M (June 1997). "Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians". Pharmacogenetics. 7 (3): 187–191. doi:10.1097/00008571-199706000-00003. PMID   9241658.
  28. ↑ Owen RP, Sangkuhl K, Klein TE, Altman RB (July 2009). "Cytochrome P450 2D6". Pharmacogenetics and Genomics. 19 (7): 559–562. doi:10.1097/FPC.0b013e32832e0e97. PMC   4373606 . PMID   19512959.
  29. ↑ Bradford LD (March 2002). "CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants". Pharmacogenomics. 3 (2): 229–243. doi:10.1517/14622416.3.2.229. PMID   11972444.
  30. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. 2007. Archived from the original on 10 October 2007. Retrieved 25 July 2010. Retrieved in July 2011
  31. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 FASS (drug formulary): Swedish environmental classification of pharmaceuticals Archived 11 June 2002 at the Wayback Machine Facts for prescribers (Fakta för förskrivare), retrieved July 2011
  32. 1 2 Leeder JS (June 2001). "Pharmacogenetics and pharmacogenomics". Pediatric Clinics of North America. 48 (3): 765–781. doi:10.1016/S0031-3955(05)70338-2. PMID   11411304.
  33. ↑ "Hydrocodone". Drugbank. Archived from the original on 6 September 2011. Retrieved 14 June 2011.
  34. ↑ Hoskins JM, Carey LA, McLeod HL (August 2009). "CYP2D6 and tamoxifen: DNA matters in breast cancer". Nature Reviews. Cancer. 9 (8): 576–586. doi:10.1038/nrc2683. PMID   19629072. S2CID   19501089.
  35. ↑ Dean L (29 June 2020). "Atomoxetine Therapy and CYP2D6 Genotype". National Center for Biotechnology Information (US). PMID   28520366 . Retrieved 24 April 2024.
  36. ↑ Brown JT, Abdel-Rahman SM, van Haandel L, Gaedigk A, Lin YS, Leeder JS (June 2016). "Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD". Clinical Pharmacology and Therapeutics. 99 (6): 642–650. doi:10.1002/cpt.319. PMC   4862932 . PMID   26660002.
  37. ↑ "Wakix pitolisant tablets Prescribing Information" (PDF). Wakix HCP. Archived (PDF) from the original on 11 January 2023. Retrieved 11 January 2023.
  38. 1 2 3 4 5 Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID   24374199.
  39. ↑ Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME (May 2021). "Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis". Scientific Reports. 11 (1): 10851. Bibcode:2021NatSR..1110851V. doi:10.1038/s41598-021-90343-y. PMC   8149637 . PMID   34035391.
  40. ↑ Shen HW, Jiang XL, Winter JC, Yu AM (October 2010). "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Current Drug Metabolism. 11 (8): 659–666. doi:10.2174/138920010794233495. PMC   3028383 . PMID   20942780.
  41. 1 2 "DILTIAZEM HCL CD- diltiazem hydrochloride capsule, coated, extended release". DailyMed. 1 February 2017. Archived from the original on 31 January 2019. Retrieved 31 January 2019.
  42. ↑ "NIFEDIPINE EXTENDED RELEASE- nifedipine tablet, extended release". DailyMed. 29 November 2012. Archived from the original on 31 January 2022. Retrieved 1 February 2019.
  43. ↑ Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, et al. (June 2005). "Inhibition of CYP2D6 activity by bupropion". Journal of Clinical Psychopharmacology. 25 (3): 226–229. doi:10.1097/01.jcp.0000162805.46453.e3. PMID   15876900. S2CID   24591644.
  44. ↑ Fasinu PS, Tekwani BL, Avula B, Chaurasiya ND, Nanayakkara NP, Wang YH, et al. (September 2016). "Pathway-specific inhibition of primaquine metabolism by chloroquine/quinine". Malaria Journal. 15 (1): 466. doi: 10.1186/s12936-016-1509-x . PMC   5020452 . PMID   27618912.
  45. ↑ "Medical Cannabis Adverse Effects & Drug Interactions" (PDF). Archived (PDF) from the original on 14 December 2019. Retrieved 28 October 2019.
  46. ↑ Zhao Y, Hellum BH, Liang A, Nilsen OG (June 2015). "Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs". Phytotherapy Research. 29 (6): 825–834. doi:10.1002/ptr.5285. PMID   25640685. S2CID   24002845.
  47. ↑ Hermann R, von Richter O (September 2012). "Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions". Planta Medica. 78 (13): 1458–1477. doi: 10.1055/s-0032-1315117 . PMID   22855269.
  48. ↑ Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, et al. (September 2018). "The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins". Chemico-Biological Interactions. 293: 115–123. Bibcode:2018CBI...293..115F. doi:10.1016/j.cbi.2018.07.022. PMID   30086269. S2CID   206489481.
  49. ↑ Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM (June 2003). "Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro". Drug Metabolism and Disposition. 31 (6): 768–772. doi:10.1124/dmd.31.6.768. PMID   12756210.
  50. 1 2 "Citalopram Oral Solution". Drugs.com. Archived from the original on 8 February 2018. Retrieved 23 January 2018.
  51. ↑ "Escitalopram-drug-information". UpToDate. Archived from the original on 28 October 2020. Retrieved 22 May 2019.
  52. 1 2 "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". FDA. 26 May 2021. Archived from the original on 4 November 2020. Retrieved 21 June 2020.
  53. ↑ Nevels RM, Weiss NH, Killebrew AE, Gontkovsky ST (July 2013). "Methylphenidate and Its Under-recognized, Under- explained, and Serious Drug Interactions: A Review of the Literature with Heightened Concerns" (PDF). German Journal of Psychiatry: 29–42. Archived from the original (PDF) on 9 April 2018. Retrieved 31 August 2016.
  54. ↑ Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD (July 1996). "Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice". Clinical Pharmacology and Therapeutics. 60 (1): 25–33. doi:10.1016/s0009-9236(96)90163-0. PMID   8689808. S2CID   1246705.
  55. ↑ Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, et al. (May 1997). "Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression". The Journal of Clinical Investigation. 99 (10): 2545–2553. doi:10.1172/jci119439. PMC   508096 . PMID   9153299.
  56. ↑ Guengerich FP, Brian WR, Iwasaki M, Sari MA, Bäärnhielm C, Berntsson P (June 1991). "Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4". Journal of Medicinal Chemistry. 34 (6): 1838–1844. doi:10.1021/jm00110a012. PMID   2061924.
  57. ↑ Owen JR, Nemeroff CB (30 May 1998). "New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine". Depression and Anxiety. 7 (Suppl 1): 24–32. doi:10.1002/(SICI)1520-6394(1998)7:1+<24::AID-DA7>3.0.CO;2-F. PMID   9597349. S2CID   34832618. Archived from the original on 1 November 2019. Retrieved 1 November 2019.
  58. ↑ Spina E, D'Arrigo C, Migliardi G, Morgante L, Zoccali R, Ancione M, et al. (August 2004). "Plasma risperidone concentrations during combined treatment with sertraline". Therapeutic Drug Monitoring. 26 (4): 386–390. doi:10.1097/00007691-200408000-00008. PMID   15257068.
  59. ↑ Sproule BA, Otton SV, Cheung SW, Zhong XH, Romach MK, Sellers EM (April 1997). "CYP2D6 inhibition in patients treated with sertraline". Journal of Clinical Psychopharmacology. 17 (2): 102–106. doi:10.1097/00004714-199704000-00007. PMID   10950472.
  60. 1 2 3 4 FASS, The Swedish official drug catalog > Kodein Recip Archived 19 July 2011 at the Wayback Machine Last reviewed 8 April 2008
  61. ↑ Shin JG, Kane K, Flockhart DA (January 2001). "Potent inhibition of CYP2D6 by haloperidol metabolites: stereoselective inhibition by reduced haloperidol". British Journal of Clinical Pharmacology. 51 (1): 45–52. doi:10.1046/j.1365-2125.2001.01313.x. PMC   2014431 . PMID   11167668.
  62. ↑ He N, Zhang WQ, Shockley D, Edeki T (February 2002). "Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes". European Journal of Clinical Pharmacology. 57 (12): 847–851. doi:10.1007/s00228-001-0399-0. PMID   11936702. S2CID   601644.
  63. ↑ Foster BC, Sockovie ER, Vandenhoek S, Bellefeuille N, Drouin CE, Krantis A, et al. (2008). "In Vitro Activity of St. John's Wort Against Cytochrome P450 Isozymes and P-Glycoprotein". Pharmaceutical Biology. 42 (2): 159–69. doi:10.1080/13880200490512034. S2CID   2366709.
  64. ↑ Gaudineau C, Auclair K (May 2004). "Inhibition of human P450 enzymes by nicotinic acid and nicotinamide". Biochemical and Biophysical Research Communications. 317 (3): 950–956. doi:10.1016/j.bbrc.2004.03.137. PMID   15081432.
  65. ↑ Briguglio M, Hrelia S, Malaguti M, Serpe L, Canaparo R, Dell'Osso B, et al. (December 2018). "Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles". Pharmaceutics. 10 (4): 277. doi: 10.3390/pharmaceutics10040277 . PMC   6321138 . PMID   30558213.
  66. ↑ Kudo S, Ishizaki T (December 1999). "Pharmacokinetics of haloperidol: an update". Clinical Pharmacokinetics. 37 (6): 435–456. doi:10.2165/00003088-199937060-00001. PMID   10628896. S2CID   71360020.
  67. ↑ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID   19948186.
  68. ↑ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID   15860375.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.