PhD Scientific Days 2026

Poster Session 2.K - Mental Health Sciences

Role of Patients’ CYP3A Status in Clozapine Pharmacokinetics: Ongoing Longitudinal Cohort Study

Name of the presenter

Tóth, Eleonóra

Institute/workplace of the presenter

Nyírő Gyula National Institute of Psychiatry and Addictions

Authors

Eleonóra Tóth MD¹, Ferenc Fekete², Katalin Monostory, PhD, DSc², Gábor Csukly, MD, PhD³
1: National Institute of Psychiatry and Addictions, Nyírő Gyula Hospital, Budapest, Hungary
2: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary
3: Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia; however, considerable interindividual variability in plasma concentrations at identical doses complicates its clinical use. Since adverse effects are more closely associated with plasma concentration than dose itself, identifying factors determining clozapine plasma levels is essential for personalised treatment.
Aims
We aimed to investigate whether baseline CYP3A status can predict the optimal clozapine dose and subsequent steady-state plasma levels in patients with schizophrenia or schizoaffective disorder according to DSM-5 criteria.
Methods
We designed a prospective longitudinal cohort study including 80–100 clozapine-naive patients with schizophrenia or schizoaffective disorder. CYP status is assessed using combined genotyping and phenotyping methods, with particular focus on CYP3A4 and CYP3A5 genotyping and CYP3A4 expression analysis from leukocytes. Clozapine plasma levels are measured after at least two weeks of unchanged dosing. Clinical effectiveness, tolerability, and relevant demographic and non-genetic variables are also recorded.
Result
Patient recruitment is ongoing, and the study protocol has been further refined to improve data collection and follow-up procedures.
Conclusion
We hypothesise that pre-treatment CYP3A status may serve as a clinically useful biomarker for predicting steady-state clozapine concentrations and supporting personalised dose optimisation.
Funding
The study is funded within the research framework of Semmelweis University without external financial support.