دورية أكاديمية
Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies.
| العنوان: | Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies. |
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| المؤلفون: | Ruan CJ; The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. Electronic address: rcjjenny@ccmu.edu.cn., Olmos I; Clinical Pharmacology Unit and Pharmacy Department, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay. Electronic address: ismael.olmos@asse.com.uy., Ricciardi C; Clinical Pharmacology Unit and Outpatient Clinic, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay. Electronic address: carinaricciardi@gmail.com., Schoretsanitis G; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA. Electronic address: george.schor@gmail.com., Vincent PD; Department of Pharmacy, Institut Universitaire en Santé Mentale de Montréal (IUSMM), Montreal, Canada; Faculty of Pharmacy, Université de Montréal, Montreal, Canada; IUSMM Research Center, Montreal, Canada. Electronic address: philippe.vincent@umontreal.ca., Anıl Yağcıoğlu AE; Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara, Turkey. Electronic address: eanil@hacettepe.edu.tr., Eap CB; Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland; Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Switzerland. Electronic address: chin.Eap@chuv.ch., Baptista T; Department of Physiology, Los Andes University Medical School, Mérida, Venezuela; Medical School, Anáhuac University, Querétaro, Mexico; Neuroorigen, Querétaro, Mexico. Electronic address: trinobaptista@gmail.com., Clark SR; University of Adelaide, Discipline of Psychiatry, Adelaide, Australia. Electronic address: scott.clark@adelaide.edu.au., Fernandez-Egea E; Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital, Fulbourn, Cambridge, UK. Electronic address: ef280@cam.ac.uk., Kim SH; Department of Psychiatry, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: sh3491@snu.ac.kr., Lane HY; Department of Psychiatry and Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan. Electronic address: hylane@gmail.com., Leung J; Department of Pharmacy, Mayo Clinic, Rochester, MN, USA. Electronic address: leung.jonathan@mayo.edu., Maroñas Amigo O; Genomic Medicine Group, Galician Public Foundation of Genomic Medicine (FPGMX), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Center for Biomedical Research in Rare Diseases Network, Carlos III Health Institute, Madrid, Spain. Electronic address: Olalla.Maronas.Amigo@sergas.es., Motuca M; Department of Psychiatry, School of Medicine at Universidad Nacional de Cuyo, Mendoza, Argentina. Electronic address: memotuca@gmail.com., Every-Palmer S; Department of Psychological Medicine, University of Otago Wellington, Wellington, New Zealand. Electronic address: susanna.every-palmer@otago.ac.nz., Procyshyn RM; Department of Psychiatry, University of British Columbia, Vancouver, Canada; British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, Canada. Electronic address: rprocyshyn@phsa.ca., Rohde C; Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: stofferrohde1@gmail.com., Suhas S; Department of Psychiatry, National Institute of Mental Health and Neurosciences [NIMHANS], Bangalore, India. Electronic address: suhasedu@yahoo.in., Schulte PFJ; Mental Health Services Noord-Holland-Noord, Alkmaar, Netherlands; Dutch Clozapine Collaboration Group, Castricum, Netherlands. Electronic address: R.Schulte@ggz-nhn.nl., Spina E; Department of Clinical and Experimeta Medicine, University of Messina, Messina, Italy. Electronic address: espina@unime.it., Takeuchi H; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. Electronic address: hirotak@dk9.so-net.ne.jp., Verdoux H; Université Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France. Electronic address: helene.verdoux@u-bordeaux.fr., Correll CU; The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. Electronic address: CCorrell@northwell.edu., Molden E; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; Department of Pharmacy, University of Oslo, Oslo, Norway. Electronic address: espen.molden@farmasi.uio.no., De Las Cuevas C; Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, University of La Laguna, Canary Islands, Spain; Instituto Universitario de Neurociencia (IUNE), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. Electronic address: cdelascuevas@gmail.com., de Leon J; Mental Health Research Center, Eastern State Hospital, Lexington, KY, USA; Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain. Electronic address: jdeleon@uky.edu. |
| المصدر: | Schizophrenia research [Schizophr Res] 2024 Jun; Vol. 268, pp. 293-301. Date of Electronic Publication: 2023 Jul 22. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Publisher B. V Country of Publication: Netherlands NLM ID: 8804207 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2509 (Electronic) Linking ISSN: 09209964 NLM ISO Abbreviation: Schizophr Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publisher B. V., c1988- |
| مواضيع طبية MeSH: | Clozapine*/blood , Clozapine*/pharmacokinetics , Clozapine*/therapeutic use , Clozapine*/analogs & derivatives , Antipsychotic Agents*/blood , Antipsychotic Agents*/pharmacokinetics , Antipsychotic Agents*/administration & dosage , Schizophrenia*/drug therapy , Schizophrenia*/blood, Humans ; Female ; Male ; Adult ; Middle Aged ; Drug Monitoring ; Medication Adherence/statistics & numerical data |
| مستخلص: | Background: Up to 1/2 of outpatients prescribed clozapine may be partially/fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial/full non-adherence are proposed a: 1) clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) clozapine/norclozapine ratio that becomes inverted; and 3) clozapine concentration that becomes non-detectable. Methods: These 3 proposed indices are based on a literature review and 17 cases of possible non-adherence from 3 samples: 1) an inpatient study in a Chinese hospital, 2) an inpatient randomized clinical trial in a United States hospital, and 3) and a Uruguayan outpatient study. Results: The first index of non-adherence is a clozapine C/D ratio which is less than half the ratio corresponding to the patient's specific ancestry group and sex-smoking subgroup. Knowing the minimum therapeutic dose of the patient based on repeated TDM makes it much easier to establish non-adherence. The second index is inverted clozapine/norclozapine ratios in the absence of alternative explanations. The third index is undetectable concentrations. By using half-lives, the chronology of the 3 indices of non-adherence was modeled in two patients: 1) the clozapine C/D ratio dropped to ≥1/2 of what is expected from the patient (around day 2); 2) the clozapine/norclozapine ratio became inverted (around day 3); and 3) the clozapine concentration became undetectable by the laboratory (around days 9-11). Conclusion: Prospective studies should further explore these proposed clozapine indices in average patients, poor metabolizers (3 presented) and ultrarapid metabolizers (2 presented). Competing Interests: Declaration of competing interest GS has received speaker/consultation fees from HLS Therapeutics and Thermo Fisher. AEAY has received speaker/advisory board fees from Janssen, Abdi İbrahim Otsuka and Nobel, and has received investigator fees from Janssen. CBE received honoraria for conferences from Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, and Zeller in the past 3 years. SRC received speaker/consultation fees from: Janssen-Cilag, Lundbeck, Otsuka and Servier and research funding from Janssen-Cilag, Lundbeck, Otsuka and Gilead. SHK has received research grants from Janssen and Dongwha. JGL has consulted/spoken on behalf of Saladax Biomedical. RMP has received speaker/consultation fees from Eisai, HLS Therapeutics, Jansen, Lundbeck, and Otsuka. HT has received grants from Daiichi Sankyo and Novartis Pharma; speaker's fees from EA. Pharma, Eisai, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, MSD, Otsuka, Sumitomo Pharma, Takeda, and Yoshitomiyakuhin; and consulting fees from Janssen, Mitsubishi Tanabe Pharma, Ono, and Sumitomo Pharma. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. In the last 3 years, the remaining authors report no conflicts of interest. (Copyright © 2023. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Clozapine/blood; Clozapine/metabolism; Clozapine/therapeutic use; Drug interaction; Medication adherence; Schizophrenia |
| المشرفين على المادة: | J60AR2IKIC (Clozapine) 0 (Antipsychotic Agents) 1I9001LWY8 (norclozapine) |
| تواريخ الأحداث: | Date Created: 20230724 Date Completed: 20240613 Latest Revision: 20240613 |
| رمز التحديث: | 20240614 |
| DOI: | 10.1016/j.schres.2023.07.002 |
| PMID: | 37487869 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1573-2509 |
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| DOI: | 10.1016/j.schres.2023.07.002 |