{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:04:16Z","timestamp":1763748256209,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"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":[[2021,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the impact of <jats:italic>cytochrome P450 2D6 (CYP2D6)<\/jats:italic> on dose\u2010adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of <jats:italic>CYP2D6*41<\/jats:italic> on dose\u2010adjusted serum concentrations in the perphenazine\u2010treated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from <jats:italic>CYP<\/jats:italic>\u2010genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose\u2010adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean dose\u2010adjusted serum concentrations of perphenazine (564 samples) were 3.9\u2010fold and 1.6\u2010fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (<jats:italic>P<\/jats:italic> &lt; .001 and <jats:italic>P<\/jats:italic> &lt; .01). For zuclopenthixol (658 samples), mean dose\u2010adjusted serum concentrations were about 1.5\u2010fold and 1.3\u2010fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (<jats:italic>P<\/jats:italic> &lt; .01 and <jats:italic>P<\/jats:italic> &lt; .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype <jats:italic>CYP2D6 *1\/*41<\/jats:italic> appears to have a similar impact on dose\u2010adjusted serum concentrations of perphenazine as <jats:italic>*1\/null<\/jats:italic> (<jats:italic>null<\/jats:italic> = variant allele encoding no enzyme function).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The <jats:italic>CYP2D6*41<\/jats:italic> allele appears to have a reduced function close to nonfunctional variant alleles.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14626","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T03:14:45Z","timestamp":1603941285000},"page":"2228-2235","source":"Crossref","is-referenced-by-count":15,"title":["Impact of <i>CYP2D6<\/i> on serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0720-1780","authenticated-orcid":false,"given":"Ragnhild Birkeland","family":"Waade","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vigdis","family":"Solhaug","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-9536","authenticated-orcid":false,"given":"Gudrun","family":"H\u00f8iseth","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"},{"name":"Department of Forensic Sciences Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Summary of product characteristics: haloperidol. Available at:https:\/\/www.ema.europa.eu\/en\/documents\/referral\/haldol-article-30-referral-annex-iii_en.pdf. Accessed March 30 2020."},{"key":"e_1_2_9_3_1","unstructured":"UpToDate. Haloperidol drug information. Available at:https:\/\/www.uptodate.com\/contents\/haloperidol-drug-information. Accessed March 30 2020."},{"key":"e_1_2_9_4_1","unstructured":"UpToDate.Perphenazine drug information. Available at:https:\/\/www.uptodate.com\/contents\/perphenazine-drug-information. Accessed March 30 2020."},{"key":"e_1_2_9_5_1","unstructured":"Lundbeck.Zuclopenthixol product monograph. Available at:https:\/\/www.lundbeck.com\/upload\/ca\/en\/files\/pdf\/pm\/Clopixol.pdf. Accessed March 30 2020."},{"key":"e_1_2_9_6_1","unstructured":"UpToDate.Zuclopenthixol drug information. Available at:https:\/\/www.uptodate.com\/contents\/zuclopenthixol-drug-information. 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