{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:36:42Z","timestamp":1791466602281,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Several publications have reported elevated clozapine concentrations in patients experiencing infections or inflammatory reactions. Proposed mechanisms include increased levels of pro\u2010inflammatory cytokines that may inhibit clozapine metabolism and enhanced binding of clozapine to the acute phase protein alpha\u20101\u2010acid glycoprotein (AGP). We collected serum samples sent to our routine laboratory over a 15\u2010month period for the analysis of clozapine. In the 1106 eligible samples, we measured AGP and C\u2010reactive protein (CRP) levels. By using a linear mixed effects regression model, we found a clear association between higher AGP and CRP levels and higher dose\u2010adjusted clozapine concentrations. As an example, an increase in the CRP level from 5 to 60\u2009mg\/L or an increase in the AGP level from 0.5 to 1.5\u2009g\/L would be expected to cause a more than twofold increase in the clozapine concentration. Our findings support and extend previous case reports and studies, suggesting that increased AGP levels during inflammatory states may play a significant role in the rise of clozapine plasma concentrations observed during illness. We propose that in addition to the clozapine concentration, CRP levels and clinical signs of adverse effects and toxicity should be closely monitored in patients with infectious or inflammatory diseases.<\/jats:p>","DOI":"10.1111\/bcpt.70208","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T02:05:12Z","timestamp":1770343512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association Between Levels of the Acute Phase Proteins Alpha\u20101\u2010Acid Glycoprotein and C\u2010Reactive Protein and Serum Concentrations of Clozapine: A Study of 1106 Therapeutic Drug Monitoring Samples"],"prefix":"10.1111","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-3328","authenticated-orcid":false,"given":"Ketil\u00a0Arne","family":"Espnes","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7902-9014","authenticated-orcid":false,"given":"Olav","family":"Spigset","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"},{"name":"Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU)  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guro\u00a0Emilie","family":"Bratt","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Tilrem","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarita","family":"Hamnes","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-0708","authenticated-orcid":false,"given":"Eirik","family":"Skogvoll","sequence":"additional","affiliation":[{"name":"Clinic of Anaesthesia and Intensive Care St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"},{"name":"Department of Circulation and Medical Imaging (ISB), Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU)  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-0413","authenticated-orcid":false,"given":"Ragnhild\u00a0Bergene","family":"Skr\u00e5stad","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology St. Olav's Hospital, Trondheim University Hospital  Trondheim Norway"},{"name":"Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU)  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00008"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.733935"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14060514"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-002-0486-x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00148-9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0867-4"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(03)00042-7"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3182666c62"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028014526701"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.151.12.1840b"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1996.00440060103013"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0313-5"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050440"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050621"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280000192"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000873"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280100375"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2146"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2003.09.010"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-100104402"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244986"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199937030-00001"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091217415621269"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41537-025-00648-4"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1625-6388"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13944"},{"key":"e_1_2_12_28_1","unstructured":"Folkehelseinstituttet \u2013 Norwegian Institute of Public Health \u201cWithdrawal of Biological Research Consent \u201d (2017) updated 2017 retrieved 2025 https:\/\/www.fhi.no\/en\/hd\/personvern\/om\u2010personvern\/biologisk\u2010forskningsreservasjon\/."},{"key":"e_1_2_12_29_1","unstructured":"Clinical Pharmacology School of Medicine Indiana University \u201cDrug Interactions Flockhart Table \u201d CYTOCHROME P450 DRUG INTERACTION TABLE (2025) retrieved September 8 2025 https:\/\/drug\u2010interactions.medicine.iu.edu\/MainTable.aspx."},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.10.029"},{"key":"e_1_2_12_31_1","unstructured":"ISO (The International Organization for Standardization) \u201cISO\/IEC 17025:2017(en) General Requirements for the Competence of Testing and Calibration Laboratories \u201d (2017) updated 2017 retrieved 2025 https:\/\/www.iso.org\/obp\/ui\/en\/#iso:std:iso\u2010iec:17025:ed\u20103:v1:en."},{"key":"e_1_2_12_32_1","unstructured":"Norwegian Accreditation \u201cNA Dok. Nr. 48a 2017 \u201d updated 2017 retrieved 2017 https:\/\/www.akkreditert.no\/en\/."},{"key":"e_1_2_12_33_1","unstructured":"The Society of Forensic Toxicologists IncandThe American Academy of Forensic Sciences \u201cToxicology Section: SOFT AAFS Forensic Laboratory Guidelines 2006 Final \u201d (2006) updated 2006 https:\/\/www.scribd.com\/doc\/55945119\/SOFT\u2010AAFS\u2010Forensic\u2010Laboratory\u2010Guidelines\u20102006\u2010Final."},{"key":"e_1_2_12_34_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) and Center for Veterinary Medicine (CVM) \u201cBioanalytical Method Validation \u2013 Guidance for Industry \u201d (2018) updated 2018 https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical\u2010Method\u2010Validation\u2010Guidance\u2010for\u2010Industry.pdf."},{"key":"e_1_2_12_35_1","unstructured":"Microsoft 365 Copilot.2025. updated 2025 retrieved 2025 https:\/\/copilot.microsoft.com\/."},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e3181acd20b"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107627"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00111.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13801"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13810"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00744-6"},{"key":"e_1_2_12_42_1","first-page":"1144","article-title":"Respiratory Infections Rather Than Antibiotics May Increase Clozapine Levels: A Critical Review of the Literature","volume":"65","author":"Leon J.","year":"2004","journal-title":"Journal of Clinical Psychiatry"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.70208","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:37:41Z","timestamp":1773027461000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.70208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/bcpt.70208"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.70208","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]},"assertion":[{"value":"2025-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70208"}}