{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T01:04:44Z","timestamp":1752282284604,"version":"3.40.5"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Clozapine is the only licensed antipsychotic for treatment-refractory schizophrenia. Therapeutic drug monitoring (TDM) refers to the measurement of clozapine concentration. Clozapine TDM can be used to optimize treatment, particularly by identifying pharmacokinetic interactions between clozapine and comedications.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We identified 5 cases of patients with available clozapine concentrations who were concomitantly receiving nifedipine and clozapine. These cases were drawn from 2 independent datasets: 2 from a double-blind, randomized clinical trial in the United States and 3 from a German TDM naturalistic database. As an index of clozapine clearance, we used the trough-level concentration-to-dose (C\/D) ratios to estimate the minimum therapeutic doses. To estimate dose-correction factors for nifedipine treatment, we included only clozapine concentrations at steady state. We divided the clozapine minimum therapeutic doses (MTD) from the on-condition by the off-nifedipine condition.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>In 4 patients, the ratio of on\/off nifedipine for MTD ranged between 0.58 and 0.82. Another patient had no data and had to be compared with published control data (female smoker of African ancestry), providing a correction factor of 0.52 after eliminating 5 concentrations contaminated by the development of obesity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>In the absence of access to TDM, when prescribing nifedipine to clozapine-treated patients, we recommend reducing the daily dose of clozapine by one-third because of the weak inhibition of clozapine metabolism. With access to TDM, TDM should guide dosing as unusual patients may need larger dose reductions, as it is possible that in some patients, nifedipine may be a moderate inhibitor requiring halving clozapine dose. Further prospective studies are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001277","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T14:04:08Z","timestamp":1731593048000},"page":"438-441","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Nifedipine May Be an Inhibitor of Clozapine Metabolism as Seen in 5 Patients: 2 From a US Double-Blind Study and 3 From a German Therapeutic Drug Monitoring Study"],"prefix":"10.1097","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-4117","authenticated-orcid":false,"given":"Georgios","family":"Schoretsanitis","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, Z\u00fcrich, Switzerland;"},{"name":"Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks;"},{"name":"Hofstra Northwell School of Medicine, Hempstead, New York;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-4148","authenticated-orcid":false,"given":"Ekkehard","family":"Haen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg;"},{"name":"Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany;"},{"name":"Clinical Pharmacology Institute AGATE gGmbH, Pentling, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-3782","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Verdoux","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, Bordeaux, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-5160","authenticated-orcid":false,"given":"Michael","family":"Paulzen","sequence":"additional","affiliation":[{"name":"Alexianer Centre for Mental Health Aachen\/Gangelt;"},{"name":"Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital RWTH Aachen;"},{"name":"JARA-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-2314","authenticated-orcid":false,"given":"Jose","family":"de Leon","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Eastern State Hospital, Lexington, Kentucky; and"},{"name":"Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"R1-20250509","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1055\/a-1625-6388","article-title":"An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels","volume":"55","author":"de Leon","year":"2022","journal-title":"Pharmacopsychiatry"},{"key":"R2-20250509","doi-asserted-by":"crossref","first-page":"19cs13169","DOI":"10.4088\/JCP.19cs13169","article-title":"Blood levels to optimize antipsychotic treatment in clinical practice: a joint consensus statement of the American Society of Clinical Psychopharmacology and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie","volume":"81","author":"Schoretsanitis","year":"2020","journal-title":"J Clin Psychiatry"},{"key":"R3-20250509","doi-asserted-by":"crossref","first-page":"e12384","DOI":"10.1111\/appy.12384","article-title":"Using therapeutic drug monitoring to personalize clozapine dosing in Asians","volume":"12","author":"de Leon","year":"2020","journal-title":"Asia Pac Psychiatry"},{"key":"R4-20250509","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/17512433.2019.1617695","article-title":"A comprehensive review of the clinical utility of and a combined analysis of the clozapine\/norclozapine ratio in therapeutic drug monitoring for adult patients","volume":"12","author":"Schoretsanitis","year":"2019","journal-title":"Expert Rev Clin Pharmacol"},{"key":"R5-20250509","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s002280050706","article-title":"Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions","volume":"55","author":"Katoh","year":"2000","journal-title":"Eur J Clin Pharmacol"},{"key":"R6-20250509","first-page":"139","article-title":"Treatment of clozapine induced hypertension and possible mechanisms","volume":"21","author":"Shiwach","year":"1998","journal-title":"Clin Neuropharmacol"},{"key":"R7-20250509","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/JCP.0000000000000926","article-title":"The effect of body weight changes on total plasma clozapine concentrations determined by applying a statistical model to the data from a double-blind trial","volume":"38","author":"Diaz","year":"2018","journal-title":"J Clin Psychopharmacol"},{"key":"R8-20250509","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.pnpbp.2005.04.031","article-title":"Does clozapine decrease smoking?","volume":"29","author":"de Leon","year":"2005","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"R9-20250509","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.schres.2023.05.010","article-title":"Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition","volume":"268","author":"Schoretsanitis","year":"2024","journal-title":"Schizophr Res"},{"key":"R10-20250509","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/JCP.0000000000001341","article-title":"European whites may need lower minimum therapeutic clozapine doses than those customarily proposed","volume":"41","author":"Schoretsanitis","year":"2021","journal-title":"J Clin Psychopharmacol"},{"key":"R11-20250509","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/bcp.15691","article-title":"A population pharmacokinetic model to guide clozapine dose selection, based on age, sex, ethnicity, body weight and smoking status","volume":"90","author":"Reeves","year":"2024","journal-title":"Br J Clin Pharmacol"},{"key":"R12-20250509","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-0043-116492","article-title":"Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017","volume":"51","author":"Hiemke","year":"2018","journal-title":"Pharmacopsychiatry"},{"key":"R13-20250509","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1055\/s-2005-862617","article-title":"Determination of five commonly used antipsychotics in human serum by high performance-liquid chromatography (HPLC) and electrochemical detection","volume":"38","author":"Bader","year":"2005","journal-title":"Pharmacopsychiatry"},{"key":"R14-20250509","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.pnpbp.2009.04.006","article-title":"Perazine elevates clozapine serum levels by inhibiting hepatic metabolism","volume":"33","author":"Schaller","year":"2009","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"R15-20250509","first-page":"151","article-title":"The management of hypertensive crises: a clinical review","volume":"160","author":"Pergolini","year":"2009","journal-title":"Clin Ter"},{"key":"R16-20250509","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00228-024-03690-w","article-title":"Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis","volume":"80","author":"Yang","year":"2024","journal-title":"Eur J Clin Pharmacol"}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000001277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T12:00:31Z","timestamp":1746792031000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000001277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,14]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000001277","relation":{},"ISSN":["0163-4356","1536-3694"],"issn-type":[{"type":"print","value":"0163-4356"},{"type":"electronic","value":"1536-3694"}],"subject":[],"published":{"date-parts":[[2024,11,14]]},"assertion":[{"value":"2024-08-04","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-20","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}