{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:52:57Z","timestamp":1783075977635,"version":"3.54.6"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p><jats:bold>Aims:<\/jats:bold> Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 (CYP) enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analysed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating comedications) or with concomitantly applied metamizole, were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose\u2010adjusted plasma concentrations.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Patients comedicated with metamizole showed &gt;50% lower plasma concentrations of quetiapine (median 45.2\u2009ng\/mL, Q<jats:sub>1<\/jats:sub>\u2009=\u200915.5; Q<jats:sub>3<\/jats:sub>\u2009=\u200990.5 <jats:italic>vs<\/jats:italic>. 92.0\u2009ng\/mL, Q<jats:sub>1<\/jats:sub>\u2009=\u200952.3; Q<jats:sub>3<\/jats:sub>\u2009=\u2009203.8, <jats:italic>P<\/jats:italic>\u2009=\u2009.003). The dose\u2010adjusted plasma concentrations were 69% lower in the comedication group (<jats:italic>P<\/jats:italic>\u2009=\u2009.001). Subgroup analyses did not suggest a dose dependency of the metamizole effect or an influence of quetiapine formulation (immediate <jats:italic>vs<\/jats:italic>. extended release). Finally, the comedication group exhibited a significantly higher proportion of patients whose quetiapine concentrations were below the therapeutic reference range (78.8% in the metamizole group <jats:italic>vs<\/jats:italic>. 54.4% in the control group, <jats:italic>P<\/jats:italic>\u2009=\u2009.037) indicating therapeutically insufficient drug concentrations.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, probably via an induction of CYP3A4. Clinicians must consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole.<\/jats:p>","DOI":"10.1111\/bcp.16168","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T12:23:45Z","timestamp":1720268625000},"page":"2793-2801","source":"Crossref","is-referenced-by-count":11,"title":["Discovering interactions in polypharmacy: Impact of metamizole on the metabolism of quetiapine"],"prefix":"10.1111","volume":"90","author":[{"given":"Fabian","family":"Watermeyer","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics University Hospital RWTH Aachen  Aachen Germany"},{"name":"JARA\u2010Translational Brain Medicine RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8816-3415","authenticated-orcid":false,"given":"Arnim Johannes","family":"Gaebler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics University Hospital RWTH Aachen  Aachen Germany"},{"name":"JARA\u2010Translational Brain Medicine RWTH Aachen University  Aachen Germany"},{"name":"Institute of Physiology University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Neuner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics University Hospital RWTH Aachen  Aachen Germany"},{"name":"JARA\u2010Translational Brain Medicine RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Haen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Clinical Pharmacology University of Regensburg  Regensburg Germany"},{"name":"Department of Pharmacology and Toxicology University of Regensburg  Regensburg Germany"},{"name":"Clinical Pharmacology Institute AGATE gGmbH  Pentling Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hiemke","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine University Medical Center of Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Schoretsanitis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics Psychiatric University Hospital Zurich  Z\u00fcrich Switzerland"},{"name":"University of Zurich  Zurich Switzerland"},{"name":"Department of Psychiatry The Zucker Hillside Hospital, Northwell Health  Glen Oaks New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-5160","authenticated-orcid":false,"given":"Michael","family":"Paulzen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics University Hospital RWTH Aachen  Aachen Germany"},{"name":"JARA\u2010Translational Brain Medicine RWTH Aachen University  Aachen Germany"},{"name":"Department of Psychiatry and Molecular Medicine Zucker School of Medicine at Hofstra\/Northwell  Hempstead New York USA"},{"name":"Alexianer Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1360"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2022.05.006"},{"key":"e_1_2_13_4_1","unstructured":"Schwalbe W\u2010DLU.:Arzneiverordnungs\u2014Report 2020. Aktuelle Daten Kosten Trends und Kommentare Springer\u2010Verlag GmbH;2020."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2008.09.026"},{"key":"e_1_2_13_6_1","first-page":"1","article-title":"Quetiapine: an objective evaluation of pharmacology, clinical uses and intoxication","volume":"8","author":"Oruch R","year":"2020","journal-title":"EC Pharmacol Toxicol"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12325"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/58.1.M76"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00482\u2010015\u20100004\u20106"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707239"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15108"},{"key":"e_1_2_13_12_1","unstructured":"European Medicines Agency.Assessment report.2018.https:\/\/www.ema.europa.eu\/en\/documents\/referral\/metamizole-article-31-referral-chmp-assessment-report_en.pdf"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00482\u2010014\u20101490\u20107"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122918"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874473711666180911091846"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000401"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100138"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14471"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2141"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2012.04304.x"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200140070\u201000003"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100031\u20101286285"},{"key":"e_1_2_13_23_1","unstructured":"FDA U.Drug development and drug interactions: table of substrates inhibitors and inducers.2019.https:\/\/www.fda.gov\/drugs\/drug-interactions-labeling\/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers"},{"key":"e_1_2_13_24_1","first-page":"142","article-title":"Richtlinie der GTFCh zur Qualit\u00e4tssicherung bei forensisch\u2010toxikologischen Untersuchungen","volume":"76","author":"Paul L","year":"2009","journal-title":"Toxichem Krimtech"},{"key":"e_1_2_13_25_1","unstructured":"US Food and Drug Administration FDA: guidance for industry on biomedical method validation.2018.http:\/\/www.fda.gov\/ucm\/groups\/fdagov-public\/@fdagov-drugs-gen\/documents\/document\/ucm070107.pdf"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100043\u2010116492"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010642\u201019844\u20101_43"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050659"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010019\u201002635\u2010y"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010014\u20101781\u2010z"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1194"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3954"},{"key":"e_1_2_13_33_1","article-title":"Bundesgesundheitsamt schr\u00e4nkt Anwendungsgebiet von Metamizol\u2010haltigen Monopr\u00e4paraten ein","volume":"83","author":"Arzneimittelkommission der deutschen \u00c4rzteschaft","year":"1986","journal-title":"Dtsch Arztebl"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1724956"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31821160c4"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.045237"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201077106\u2010x"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2005.02507.x"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301646"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000413"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2005.27.5.908643"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/63.7.764"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00886"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270003256059"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881104042632"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000070"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.129"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:47:11Z","timestamp":1730296031000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,6]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/bcp.16168"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16168","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,6]]}}}