{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:18:45Z","timestamp":1789543125343,"version":"build-2803163510"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5\u2010HT<jats:sub>2a\/2c<\/jats:sub>), dopamine (D<jats:sub>2<\/jats:sub>) and histamine (H<jats:sub>1<\/jats:sub>) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5\u2010HT<jats:sub>2c<\/jats:sub>\u2010receptor and less H<jats:sub>1<\/jats:sub> blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross\u2010sectional study in 39 patients (female <jats:italic>n<\/jats:italic>\u2009=\u20098 (20.5%), smokers <jats:italic>n<\/jats:italic>\u2009=\u200918 (46.2%), average age 45.8\u2009\u00b1\u20099.9\u00a0years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (<jats:italic>r<\/jats:italic>\u2009=\u20090.354, <jats:italic>P<\/jats:italic>\u2009=\u2009.03) and hemoglobin A1c (HbA1c) (<jats:italic>r<\/jats:italic>\u2009=\u20090.34, <jats:italic>P<\/jats:italic>\u2009=\u2009.03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (<jats:italic>r<\/jats:italic>\u2009=\u20090.723, <jats:italic>P<\/jats:italic>\u2009=\u2009.001), HbA1c (r\u2009=\u20090.49, <jats:italic>P<\/jats:italic>\u2009=\u2009.04) and BMI (<jats:italic>r<\/jats:italic>\u2009=\u20090.63, <jats:italic>P<\/jats:italic>\u2009=\u2009.004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.<\/jats:p>","DOI":"10.1111\/bcp.14992","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T11:12:47Z","timestamp":1626693167000},"page":"853-857","source":"Crossref","is-referenced-by-count":16,"title":["Body weight gain in clozapine\u2010treated patients: Is norclozapine the culprit?"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-1259","authenticated-orcid":false,"given":"Naomi T.","family":"Jessurun","sequence":"first","affiliation":[{"name":"Netherlands Pharmacovigilance Centre Lareb  Hertogenbosch the Netherlands"},{"name":"Unit of PharmacoTherapy, Epidemiology &amp; \u2010Economics, Faculty of Science and Engineering University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hieronymus J.","family":"Derijks","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jeroen Bosch Hospital  Hertogenbosch the Netherlands"},{"name":"Department of Pharmacy Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-532X","authenticated-orcid":false,"given":"Rob J.","family":"van Marum","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Jeroen Bosch Hospital  Hertogenbosch the Netherlands"},{"name":"Department of Elderly Care Medicine\/Amsterdam Public Health Research Institute Amsterdam UMC, location VUmc  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Jongkind","sequence":"additional","affiliation":[{"name":"Reinier van Arkel Mental Health Institute  Hertogenbosch the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline L.","family":"Giraud","sequence":"additional","affiliation":[{"name":"Netherlands Pharmacovigilance Centre Lareb  Hertogenbosch the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eug\u00e8ne P.","family":"van Puijenbroek","sequence":"additional","affiliation":[{"name":"Netherlands Pharmacovigilance Centre Lareb  Hertogenbosch the Netherlands"},{"name":"Unit of PharmacoTherapy, Epidemiology &amp; \u2010Economics, Faculty of Science and Engineering University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen P.","family":"Grootens","sequence":"additional","affiliation":[{"name":"Reinier van Arkel Mental Health Institute  Hertogenbosch the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881107075509"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596300-000000000-00000"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.05.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n0607"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000476"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9127-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e31802e513a"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pra.0000358312.99233.ef"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apnu.2008.06.007"},{"issue":"1","key":"e_1_2_9_11_1","first-page":"S297","article-title":"The Concise Guide to Pharmacology 2019\/20: Enzymes","volume":"176","author":"Alexander SPH","year":"2019","journal-title":"Br J Pharmacol"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14992","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14992","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T04:13:44Z","timestamp":1692850424000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,5]]},"references-count":10,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/bcp.14992"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14992","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,5]]}}}