The Potential Role of POR*28 and CYP1A2*F Genetic Variations and Lifestyle Factors on Clozapine and N-DesmethylClozapine Plasma Levels in Schizophrenia Patients

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dc.authoridBASKAK, BORA/0000-0002-0723-4446
dc.authoridDural, Emrah/0000-0002-9320-8008
dc.authoridDEMIRBUGEN OZ, MERVE/0000-0002-8484-1207
dc.authoridTok, Kenan Can/0000-0002-9353-8867
dc.authoridGUMUSTAS, MEHMET/0000-0002-4846-5398
dc.authoridGumustas, Mehmet/0000-0003-2793-7154
dc.authoridKir, Yagmur/0000-0002-4234-1394
dc.contributor.authorOz, Merve Demirbugen
dc.contributor.authorOzdemir, Fezile
dc.contributor.authorTok, Kenan Can
dc.contributor.authorDural, Emrah
dc.contributor.authorKir, Yagmur
dc.contributor.authorUlusoy, Muge
dc.contributor.authorGumustas, Mehmet
dc.date.accessioned2024-10-26T18:10:54Z
dc.date.available2024-10-26T18:10:54Z
dc.date.issued2023
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractBackground: Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects. Research design and methods: As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method. Results: The patients' CYP1A2 and POR genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis, POR *28 genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption. Conclusions: The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making.
dc.description.sponsorshipAnkara University Scientific Projects Coordination Unit [18L0217001]
dc.description.sponsorshipThis study was supported by a Grant from the Ankara University Scientific Projects Coordination Unit [18L0217001].
dc.identifier.doi10.1080/17425255.2023.2221849
dc.identifier.endpage327
dc.identifier.issn1742-5255
dc.identifier.issn1744-7607
dc.identifier.issue5
dc.identifier.pmid37269349
dc.identifier.scopus2-s2.0-85161527443
dc.identifier.scopusqualityQ1
dc.identifier.startpage319
dc.identifier.urihttps://doi.org/10.1080/17425255.2023.2221849
dc.identifier.urihttps://hdl.handle.net/20.500.12418/30437
dc.identifier.volume19
dc.identifier.wosWOS:001002483200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofExpert Opinion on Drug Metabolism & Toxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectClozapine
dc.subjectCYP1A2
dc.subjectCytochrome P450 oxidoreductase (POR)
dc.subjectdrug metabolism
dc.subjectpharmacogenetics
dc.subjectprecision medicine
dc.titleThe Potential Role of POR*28 and CYP1A2*F Genetic Variations and Lifestyle Factors on Clozapine and N-DesmethylClozapine Plasma Levels in Schizophrenia Patients
dc.typeArticle

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