The effects of UGT1A4 and ABCB1 polymorphisms on clozapine and Ndesmethyl clozapine plasma levels in Turkish schizophrenia patients

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dc.authoridTok, Kenan Can/0000-0002-9353-8867
dc.contributor.authorOzdemir, Fezile
dc.contributor.authorOz, Merve Demirbugen
dc.contributor.authorTok, Kenan Can
dc.contributor.authorDural, Emrah
dc.contributor.authorKir, Yagmur
dc.contributor.authorGumustas, Mehmet
dc.contributor.authorBaskak, Bora
dc.date.accessioned2025-05-04T16:46:59Z
dc.date.available2025-05-04T16:46:59Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractClozapine (CLZ) is an antipsychotic which is particularly used in treatment resistant schizophrenia patients who do not respond to other agents. It is preferred because it reduces suicidal behaviours and attempts, reducing aggression and violent behaviour. The aim of the study is to evaluate the effects of ABCB1 rs1045642 and UGT1A4 rs2011425 polymorphisms on CLZ and its major metabolite Ndesmethly clozapine (DCLZ) plasma concentrations in patients with schizophrenia. A total 109 of Turkish patients with schizophrenia on continually administered CLZ monotherapy were included. The plasma concentrations of CLZ and DCLZ were measured using an HPLC after liquid-liquid extraction while, transporter gene ABCB1 and phase two enzyme UGT1A4 polymorphisms were identified using PCR- RFLP method. Results showed that UGT1A4*3 polymorphism has statistically significant effects on CLZ C/D and DCLZ C/D levels in patients with sub/supra therapeutic levels while ABCB1 C3435T polymorphism has a significant effect on CLZ/DCLZ ratio among patients who have subtherapeutic levels. This study indicates the influence of genetic differences on plasma levels and highlights the importance of pharmacogenetic studies in clinic. Using the obtained results as pharmacogenetic biomarkers will help clinicians provide effective treatment in individual patients and reduce the undesirable side effects.
dc.description.sponsorshipAnkara University Scientific Projects Coordination Unit [18 L0217001]
dc.description.sponsorshipThis study was supported by a Grant from the Ankara University Scientific Projects Coordination Unit [18 L0217001] .
dc.identifier.doi10.1016/j.taap.2024.117219
dc.identifier.issn0041-008X
dc.identifier.issn1096-0333
dc.identifier.pmid39761923
dc.identifier.scopus2-s2.0-85214313861
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1016/j.taap.2024.117219
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35444
dc.identifier.volume495
dc.identifier.wosWOS:001411256700001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofToxicology and Applied Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectABCB1
dc.subjectClozapine
dc.subjectSchizophrenia
dc.subjectTurkish
dc.titleThe effects of UGT1A4 and ABCB1 polymorphisms on clozapine and Ndesmethyl clozapine plasma levels in Turkish schizophrenia patients
dc.typeArticle

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