Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study
Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in...
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| Veröffentlicht in: | Pharmacogenomics 2017-04, Vol.18 (5), p.433-443 |
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| creator | Chaudhry, Mamoonah Alessandrini, Marco Rademan, Jacobus Dodgen, Tyren M Steffens, Francois E van Zyl, Danie G Gaedigk, Andrea Pepper, Michael S |
| description | Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.
To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.
Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.
Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings. |
| doi_str_mv | 10.2217/pgs-2016-0185 |
| format | Article |
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To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.
Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.
Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.</description><identifier>ISSN: 1462-2416</identifier><identifier>EISSN: 1744-8042</identifier><identifier>DOI: 10.2217/pgs-2016-0185</identifier><identifier>PMID: 28350251</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Amitriptyline ; Amitriptyline - metabolism ; Amitriptyline - therapeutic use ; Analgesics, Non-Narcotic - metabolism ; Analgesics, Non-Narcotic - therapeutic use ; Antidepressants ; Consortia ; Constipation ; CYP2D6 protein ; Cytochrome ; Cytochrome P-450 CYP2D6 - genetics ; Cytochrome P-450 CYP2D6 - metabolism ; Cytochrome P450 ; Diabetes ; Diabetes mellitus ; Diabetic Neuropathies - diagnosis ; Diabetic Neuropathies - drug therapy ; Diabetic Neuropathies - genetics ; Diabetic neuropathy ; Drug dosages ; Drug metabolism ; Drug therapy ; Genetic diversity ; Genotype ; Genotype & phenotype ; Genotypes ; Humans ; Metabolism ; Metabolites ; Pain ; Patients ; Peripheral neuropathy ; Phenotypes ; Pilot Projects ; Public health ; Random Allocation ; Treatment Outcome</subject><ispartof>Pharmacogenomics, 2017-04, Vol.18 (5), p.433-443</ispartof><rights>2017. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-f7bec029e9af8867deb788b8ae2e7f7a753b543aa4a39645618c8e37d132a6ae3</citedby><cites>FETCH-LOGICAL-c360t-f7bec029e9af8867deb788b8ae2e7f7a753b543aa4a39645618c8e37d132a6ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28350251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chaudhry, Mamoonah</creatorcontrib><creatorcontrib>Alessandrini, Marco</creatorcontrib><creatorcontrib>Rademan, Jacobus</creatorcontrib><creatorcontrib>Dodgen, Tyren M</creatorcontrib><creatorcontrib>Steffens, Francois E</creatorcontrib><creatorcontrib>van Zyl, Danie G</creatorcontrib><creatorcontrib>Gaedigk, Andrea</creatorcontrib><creatorcontrib>Pepper, Michael S</creatorcontrib><title>Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study</title><title>Pharmacogenomics</title><addtitle>Pharmacogenomics</addtitle><description>Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.
To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.
Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.
Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. 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metabolism</topic><topic>Amitriptyline - therapeutic use</topic><topic>Analgesics, Non-Narcotic - metabolism</topic><topic>Analgesics, Non-Narcotic - therapeutic use</topic><topic>Antidepressants</topic><topic>Consortia</topic><topic>Constipation</topic><topic>CYP2D6 protein</topic><topic>Cytochrome</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Cytochrome P-450 CYP2D6 - metabolism</topic><topic>Cytochrome P450</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic Neuropathies - diagnosis</topic><topic>Diabetic Neuropathies - drug therapy</topic><topic>Diabetic Neuropathies - genetics</topic><topic>Diabetic neuropathy</topic><topic>Drug dosages</topic><topic>Drug metabolism</topic><topic>Drug therapy</topic><topic>Genetic diversity</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Genotypes</topic><topic>Humans</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Pain</topic><topic>Patients</topic><topic>Peripheral neuropathy</topic><topic>Phenotypes</topic><topic>Pilot Projects</topic><topic>Public health</topic><topic>Random Allocation</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chaudhry, Mamoonah</creatorcontrib><creatorcontrib>Alessandrini, Marco</creatorcontrib><creatorcontrib>Rademan, Jacobus</creatorcontrib><creatorcontrib>Dodgen, Tyren M</creatorcontrib><creatorcontrib>Steffens, Francois E</creatorcontrib><creatorcontrib>van Zyl, Danie G</creatorcontrib><creatorcontrib>Gaedigk, Andrea</creatorcontrib><creatorcontrib>Pepper, Michael S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>UK & Ireland Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Pharmacogenomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chaudhry, Mamoonah</au><au>Alessandrini, Marco</au><au>Rademan, Jacobus</au><au>Dodgen, Tyren M</au><au>Steffens, Francois E</au><au>van Zyl, Danie G</au><au>Gaedigk, Andrea</au><au>Pepper, Michael S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study</atitle><jtitle>Pharmacogenomics</jtitle><addtitle>Pharmacogenomics</addtitle><date>2017-04</date><risdate>2017</risdate><volume>18</volume><issue>5</issue><spage>433</spage><epage>443</epage><pages>433-443</pages><issn>1462-2416</issn><eissn>1744-8042</eissn><abstract>Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.
To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.
Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.
Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>28350251</pmid><doi>10.2217/pgs-2016-0185</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amitriptyline Amitriptyline - metabolism Amitriptyline - therapeutic use Analgesics, Non-Narcotic - metabolism Analgesics, Non-Narcotic - therapeutic use Antidepressants Consortia Constipation CYP2D6 protein Cytochrome Cytochrome P-450 CYP2D6 - genetics Cytochrome P-450 CYP2D6 - metabolism Cytochrome P450 Diabetes Diabetes mellitus Diabetic Neuropathies - diagnosis Diabetic Neuropathies - drug therapy Diabetic Neuropathies - genetics Diabetic neuropathy Drug dosages Drug metabolism Drug therapy Genetic diversity Genotype Genotype & phenotype Genotypes Humans Metabolism Metabolites Pain Patients Peripheral neuropathy Phenotypes Pilot Projects Public health Random Allocation Treatment Outcome |
| title | Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study |
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