{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:51:34Z","timestamp":1783075894721,"version":"3.54.6"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T00:00:00Z","timestamp":1488412800000},"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":[[2017,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although clinically widespread, scientific evidence for antipsychotic polypharmacy is still limited. Combining different drugs increases the potential for drug\u2013drug interactions, enhancing the risk of adverse drug reactions. We aimed to unravel the potential pharmacokinetic interactions between risperidone (RIS) and perazine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a therapeutic drug monitoring database containing plasma concentrations of RIS and its active metabolite [9\u2010hydroxyrisperidone (9\u2010OH\u2010RIS)], we considered two groups: a group of patients under antipsychotic monotherapy with RIS (<jats:italic>n<\/jats:italic>\u00a0=\u00a040) and a group of patients that was comedicated with perazine (<jats:italic>n<\/jats:italic>\u00a0=\u00a016). Groups were matched for demographic characteristics and daily dosage of RIS. Plasma concentrations, concentrations corrected for the dose (C\/D) of RIS, 9\u2010OH\u2010RIS and the active moiety (RIS\u00a0+\u00a09\u2010OH\u2010RIS), as well as the metabolic ratios of concentrations of 9\u2010OH\u2010RIS\/RIS, were compared using nonparametric tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All parameters other than plasma concentrations and the C\/D ratio of 9\u2010OH\u2010RIS differed between groups. Median values for plasma concentrations of the active moiety and C\/D of the active moiety were higher in the perazine group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, respectively). Differences were driven by variations in the plasma concentrations and C\/D of RIS, which were higher in the perazine group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, respectively). Metabolic ratios were lower in the perazine group (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The coadministration of perazine in RIS\u2010medicated patients leads to significantly higher plasma concentrations and C\/D values of RIS and its active moiety, and a lower metabolic ratio, reflecting the cytochrome P450 (CYP) 2D6 phenotype. We suggest that the mechanism underlying the effect of perazine on RIS metabolism is based on an inhibition of CYP2D6 and CYP3A4 activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13255","type":"journal-article","created":{"date-parts":[[2017,2,4]],"date-time":"2017-02-04T15:42:38Z","timestamp":1486222958000},"page":"1668-1675","source":"Crossref","is-referenced-by-count":13,"title":["Cytochrome P450\u2010mediated interaction between perazine and risperidone: implications for antipsychotic polypharmacy"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-5160","authenticated-orcid":false,"given":"Michael","family":"Paulzen","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, and JARA \u2013 Translational Brain Medicine RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Haen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology University of Regensburg Regensburg 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":"Benedikt","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology University of Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Lammertz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, and JARA \u2013 Translational Brain Medicine RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Gr\u00fcnder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, and JARA \u2013 Translational Brain Medicine RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-4117","authenticated-orcid":false,"given":"Georgios","family":"Schoretsanitis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, and JARA \u2013 Translational Brain Medicine RWTH Aachen University Aachen Germany"},{"name":"University Hospital of Psychiatry Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-006-9063-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2012.03.018"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.54.1.55"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-015-0559-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(85)90174-X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712000399"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0701"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000131"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881116650390"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000601"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000576"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.13.1652"},{"key":"e_1_2_10_17_1","first-page":"1: CD002832","article-title":"Perazine for schizophrenia","author":"Leucht S","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(03)00105-6"},{"key":"e_1_2_10_19_1","first-page":"449","article-title":"Distribution interactions between perazine and antidepressant drugs. In vivo studies","volume":"52","author":"Wojcikowski J","year":"2000","journal-title":"Pol J Pharmacol"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3007-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2009.04.006"},{"key":"e_1_2_10_22_1","first-page":"872","article-title":"Interactions between neuroleptics and CYP2C6 in rat liver \u2013in vitro and ex vivo study","volume":"57","author":"Haduch A","year":"2005","journal-title":"Pharmacol Rep"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0022-3565(25)24408-1","article-title":"Pharmacology of risperidone (R 64 766), a new antipsychotic with serotonin\u2010S2 and dopamine\u2010D2 antagonistic properties","volume":"244","author":"Janssen PA","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v58n1205"},{"issue":"3","key":"e_1_2_10_25_1","first-page":"S89","article-title":"Clinical review of risperidone","volume":"38","author":"Chouinard G","year":"1993","journal-title":"Can J Psychiatry"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(98)00105-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005334"},{"key":"e_1_2_10_28_1","first-page":"1263","article-title":"Different enantioselective 9\u2010hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes","volume":"29","author":"Yasui\u2010Furukori N","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009347867"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1286287"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.12.016"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2085-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2016.07.009"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2016.1154043"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-016-0736-z"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1286285"},{"key":"e_1_2_10_37_1","first-page":"238","article-title":"Arzneimitteltherapiesicherheit\/Pharmakovigilanz in der klinischen Psychopharmakotherapie\u2013Das Kliniknetzwerk AGATE","volume":"18","author":"Haen E","year":"2011","journal-title":"Psychopharmakotherapie"},{"key":"e_1_2_10_38_1","unstructured":"US Food and Drug Administration.Drug development and drug interactions: table of substrates inhibitors and inducers[online]. Available athttp:\/\/www.fda.gov\/Drugs\/DevelopmentApprovalProcess\/DevelopmentResources\/DrugInteractionsLabeling\/ucm093664.htm(last accessed 01 January 2017)."},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-862617"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973836"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199902000-00017"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v66n0103"},{"key":"e_1_2_10_43_1","doi-asserted-by":"crossref","unstructured":"PodeaDM SabauAI WildKJ.Comorbid Anxiety in Schizophrenia and Schizoaffective Disorder A Fresh Look at Anxiety Disorders Dr. Federico Durbano (Ed.) InTech2015. doi:10.5772\/60643. Available athttp:\/\/www.intechopen.com\/.","DOI":"10.5772\/60643"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032424"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2004.05.008"},{"key":"e_1_2_10_46_1","first-page":"615","article-title":"Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver","volume":"53","author":"Daniel WA","year":"2001","journal-title":"Pol J Pharmacol"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000489"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph7010325"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13255","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:09:39Z","timestamp":1749946179000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,2]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1111\/bcp.13255"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13255","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,2]]}}}