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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

dc.rights.licenseopenen_US
dc.contributor.authorRUAN, Can-Jun
dc.contributor.authorOLMOS, Ismael
dc.contributor.authorRICCIARDI, Carina
dc.contributor.authorSCHORETSANITIS, Georgios
dc.contributor.authorVINCENT, Philippe D
dc.contributor.authorANIL YAĞCIOĞLU, A Elif
dc.contributor.authorEAP, Chin B
dc.contributor.authorBAPTISTA, Trino
dc.contributor.authorCLARK, Scott R
dc.contributor.authorFERNANDEZ-EGEA, Emilio
dc.contributor.authorKIM, Se Hyun
dc.contributor.authorLANE, Hsien-Yuan
dc.contributor.authorLEUNG, Jonathan
dc.contributor.authorMAROÑAS AMIGO, Olalla
dc.contributor.authorMOTUCA, Mariano
dc.contributor.authorEVERY-PALMER, Susanna
dc.contributor.authorPROCYSHYN, Ric M
dc.contributor.authorROHDE, Christopher
dc.contributor.authorSUHAS, Satish
dc.contributor.authorSCHULTE, Peter F J
dc.contributor.authorSPINA, Edoardo
dc.contributor.authorTAKEUCHI, Hiroyoshi
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorVERDOUX, Helene
dc.contributor.authorCORRELL, Christoph U
dc.contributor.authorMOLDEN, Espen
dc.contributor.authorDE LAS CUEVAS, Carlos
dc.contributor.authorDE LEON, Jose
dc.date.accessioned2023-10-17T09:48:35Z
dc.date.available2023-10-17T09:48:35Z
dc.date.issued2023-07-22
dc.identifier.issn1573-2509en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184456
dc.description.abstractEnUp 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. 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. 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). Prospective studies should further explore these proposed clozapine indices in average patients, poor metabolizers (3 presented) and ultrarapid metabolizers (2 presented).
dc.language.isoENen_US
dc.subject.enClozapine/blood
dc.subject.enClozapine/metabolism
dc.subject.enClozapine/therapeutic use
dc.subject.enDrug interaction
dc.subject.enMedication adherence
dc.subject.enSchizophrenia
dc.title.enExploring 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
dc.title.alternativeSchizophr Resen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.schres.2023.07.002en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37487869en_US
bordeaux.journalSchizophrenia Researchen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamAHEADen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04245813
hal.version1
hal.date.transferred2023-10-17T09:48:38Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Schizophrenia%20Research&rft.date=2023-07-22&rft.eissn=1573-2509&rft.issn=1573-2509&rft.au=RUAN,%20Can-Jun&OLMOS,%20Ismael&RICCIARDI,%20Carina&SCHORETSANITIS,%20Georgios&VINCENT,%20Philippe%20D&rft.genre=article


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