PhD Scientific Days 2025

Poster Session II. - L: Mental Health Sciences

Role of CYP3A status in the pharmacokinetics of clozapine - protocol for a longitudinal cohort study

Name of the presenter

Tóth Eleonóra

Institute/workplace of the presenter

Nyírő Gyula National Institute of Psychiatry and Addictions

Authors

Eleonóra Tóth¹, Katalin Monostory², Gábor Csukly³

1: Nyírő Gyula National Institute of Psychiatry and Addictions
2: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences
3: Semmelweis University, Department of Psychiatry and Psychotherapy

Text of the abstract

In our study, we aim to apply genetic methods—specifically the combined genotyping and phenotyping of CYP enzymes—to support the everyday clinical management of psychiatric patients and to contribute to the development of personalised therapeutic strategies.
The primary objective of the study is to confirm that a safe and effective clozapine dose can be predicted in patients with schizophrenia based on their CYP3A status, particularly in those with impaired CYP1A2 function. Additionally, we aim to investigate potential changes in CYP3A status in ‘clozapine-naive’ patients following the initiation and adjustment of clozapine therapy. To further support the development of personalised pharmacotherapy, we also intend to predict the expected antipsychotic response through baseline EEG assessments.
Throughout the study, clozapine plasma levels and CYP3A status will be determined from blood samples. Measurement of clozapine levels will be part of routine clinical care, serving the purpose of individualised dose optimisation, while CYP3A status will be assessed using residual blood samples collected during standard blood draws required for clozapine treatment.
In parallel, we will monitor treatment efficacy and potential side effects using standardised clinical scales. We will also collect a range of demographic and non-genetic data—such as age, smoking habits, and comorbidities—which have been reported in the literature to influence CYP enzyme activity.
Based on prior findings from our research group, which showed a strong correlation between CYP3A4 expression at steady-state and clozapine plasma levels, we hypothesise that pre-treatment CYP3A status may predict subsequent steady-state clozapine concentrations. Ultimately, we aim to identify a combination of baseline characteristics—including demographic, clinical, electrophysiological, and pharmacogenetic markers—that can reliably predict individual response to clozapine therapy.
The study is funded exclusively through the research framework provided by Semmelweis University, with no additional external funding involved.