Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study
The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the m...
Gespeichert in:
| Veröffentlicht in: | British journal of clinical pharmacology 2021-03, Vol.87 (3), p.1529-1532 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1532 |
|---|---|
| container_issue | 3 |
| container_start_page | 1529 |
| container_title | British journal of clinical pharmacology |
| container_volume | 87 |
| creator | Jessurun, Naomi T. Vermeulen Windsant, Annemieke Mikes, Oenone Puijenbroek, Eugène P. Marum, Rob J. Grootens, Koen Derijks, Hieronymus J. |
| description | The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline ( |
| doi_str_mv | 10.1111/bcp.14455 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_wiley_primary_10_1111_bcp_14455_BCP14455</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>BCP14455</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3605-a5716e1efb7affa57e8f37056cc6eadb4960460efaf6fa4ea4c740d3c94e76033</originalsourceid><addsrcrecordid>eNp10LlOxDAQBmALgWA5Cl4AuYQiYMdHoITllJCggIIqcpwxMeSS7d0lHY9Ax_vxJBgCdEwzGunTr9GP0DYl-zTOQaH7fcq5EEtoQpkUSUpTsYwmhBGZiFTQNbTu_RMhlFEpVtEaS2VKBecT9H7VVrawwXYt7gyePtympxIvbKhw3S1w2XnAuwI3j3u4V657gWBbwLaNV7DQBj_ayj5WmJKP17dqKCMb2s4FZ_sw1F_eg5s1uIY51D6aY9y7zvegg50D7ivlGqW75yiD1diHWTlsohWjag9bP3sD3Z-f3U0vk-ubi6vp8XWimSQiUSKjEiiYIlPGxAsODcuIkFpLUGXBjyThkoBRRhrFQXGdcVIyfcQhk4SxDbQ35ur4kXdg8t7ZRrkhpyT_KjeP5ebf5Ua7M9p-VjRQ_snfNiM4GMHC1jD8n5SfTG_HyE-cPIjY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study</title><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Jessurun, Naomi T. ; Vermeulen Windsant, Annemieke ; Mikes, Oenone ; Puijenbroek, Eugène P. ; Marum, Rob J. ; Grootens, Koen ; Derijks, Hieronymus J.</creator><creatorcontrib>Jessurun, Naomi T. ; Vermeulen Windsant, Annemieke ; Mikes, Oenone ; Puijenbroek, Eugène P. ; Marum, Rob J. ; Grootens, Koen ; Derijks, Hieronymus J.</creatorcontrib><description>The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/bcp.14455</identifier><identifier>PMID: 32621544</identifier><language>eng</language><publisher>England</publisher><subject>CYP2D6 ; hydroxynortriptyline ; nortriptyline ; paroxetine addition ; phenoconversion</subject><ispartof>British journal of clinical pharmacology, 2021-03, Vol.87 (3), p.1529-1532</ispartof><rights>2020 The British Pharmacological Society</rights><rights>2020 The British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3605-a5716e1efb7affa57e8f37056cc6eadb4960460efaf6fa4ea4c740d3c94e76033</citedby><cites>FETCH-LOGICAL-c3605-a5716e1efb7affa57e8f37056cc6eadb4960460efaf6fa4ea4c740d3c94e76033</cites><orcidid>0000-0002-8267-1259 ; 0000-0003-4292-532X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbcp.14455$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbcp.14455$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32621544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jessurun, Naomi T.</creatorcontrib><creatorcontrib>Vermeulen Windsant, Annemieke</creatorcontrib><creatorcontrib>Mikes, Oenone</creatorcontrib><creatorcontrib>Puijenbroek, Eugène P.</creatorcontrib><creatorcontrib>Marum, Rob J.</creatorcontrib><creatorcontrib>Grootens, Koen</creatorcontrib><creatorcontrib>Derijks, Hieronymus J.</creatorcontrib><title>Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges.</description><subject>CYP2D6</subject><subject>hydroxynortriptyline</subject><subject>nortriptyline</subject><subject>paroxetine addition</subject><subject>phenoconversion</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10LlOxDAQBmALgWA5Cl4AuYQiYMdHoITllJCggIIqcpwxMeSS7d0lHY9Ax_vxJBgCdEwzGunTr9GP0DYl-zTOQaH7fcq5EEtoQpkUSUpTsYwmhBGZiFTQNbTu_RMhlFEpVtEaS2VKBecT9H7VVrawwXYt7gyePtympxIvbKhw3S1w2XnAuwI3j3u4V657gWBbwLaNV7DQBj_ayj5WmJKP17dqKCMb2s4FZ_sw1F_eg5s1uIY51D6aY9y7zvegg50D7ivlGqW75yiD1diHWTlsohWjag9bP3sD3Z-f3U0vk-ubi6vp8XWimSQiUSKjEiiYIlPGxAsODcuIkFpLUGXBjyThkoBRRhrFQXGdcVIyfcQhk4SxDbQ35ur4kXdg8t7ZRrkhpyT_KjeP5ebf5Ua7M9p-VjRQ_snfNiM4GMHC1jD8n5SfTG_HyE-cPIjY</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Jessurun, Naomi T.</creator><creator>Vermeulen Windsant, Annemieke</creator><creator>Mikes, Oenone</creator><creator>Puijenbroek, Eugène P.</creator><creator>Marum, Rob J.</creator><creator>Grootens, Koen</creator><creator>Derijks, Hieronymus J.</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-8267-1259</orcidid><orcidid>https://orcid.org/0000-0003-4292-532X</orcidid></search><sort><creationdate>202103</creationdate><title>Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study</title><author>Jessurun, Naomi T. ; Vermeulen Windsant, Annemieke ; Mikes, Oenone ; Puijenbroek, Eugène P. ; Marum, Rob J. ; Grootens, Koen ; Derijks, Hieronymus J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3605-a5716e1efb7affa57e8f37056cc6eadb4960460efaf6fa4ea4c740d3c94e76033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>CYP2D6</topic><topic>hydroxynortriptyline</topic><topic>nortriptyline</topic><topic>paroxetine addition</topic><topic>phenoconversion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jessurun, Naomi T.</creatorcontrib><creatorcontrib>Vermeulen Windsant, Annemieke</creatorcontrib><creatorcontrib>Mikes, Oenone</creatorcontrib><creatorcontrib>Puijenbroek, Eugène P.</creatorcontrib><creatorcontrib>Marum, Rob J.</creatorcontrib><creatorcontrib>Grootens, Koen</creatorcontrib><creatorcontrib>Derijks, Hieronymus J.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jessurun, Naomi T.</au><au>Vermeulen Windsant, Annemieke</au><au>Mikes, Oenone</au><au>Puijenbroek, Eugène P.</au><au>Marum, Rob J.</au><au>Grootens, Koen</au><au>Derijks, Hieronymus J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2021-03</date><risdate>2021</risdate><volume>87</volume><issue>3</issue><spage>1529</spage><epage>1532</epage><pages>1529-1532</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges.</abstract><cop>England</cop><pmid>32621544</pmid><doi>10.1111/bcp.14455</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-8267-1259</orcidid><orcidid>https://orcid.org/0000-0003-4292-532X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0306-5251 |
| ispartof | British journal of clinical pharmacology, 2021-03, Vol.87 (3), p.1529-1532 |
| issn | 0306-5251 1365-2125 |
| language | eng |
| recordid | cdi_wiley_primary_10_1111_bcp_14455_BCP14455 |
| source | Wiley Online Library Journals Frontfile Complete; Wiley Free Content; EZB-FREE-00999 freely available EZB journals |
| subjects | CYP2D6 hydroxynortriptyline nortriptyline paroxetine addition phenoconversion |
| title | Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T03%3A04%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20CYP2D6%20with%20low%20dose%20(5%20mg)%20paroxetine%20in%20patients%20with%20high%2010%E2%80%90hydroxynortriptyline%20serum%20levels%E2%80%90A%20prospective%20pharmacokinetic%20study&rft.jtitle=British%20journal%20of%20clinical%20pharmacology&rft.au=Jessurun,%20Naomi%20T.&rft.date=2021-03&rft.volume=87&rft.issue=3&rft.spage=1529&rft.epage=1532&rft.pages=1529-1532&rft.issn=0306-5251&rft.eissn=1365-2125&rft_id=info:doi/10.1111/bcp.14455&rft_dat=%3Cwiley_cross%3EBCP14455%3C/wiley_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/32621544&rfr_iscdi=true |