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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1518739

The effects of clinical and pharmacological factors on the ratio of clozapine to norclozapine in psychiatric patients

Provisionally accepted
Anna Mach Anna Mach 1Anna Wnorowska Anna Wnorowska 1*Marcin Siwek Marcin Siwek 2Marcin Wojnar Marcin Wojnar 1,3Maria Radziwon-Zaleska Maria Radziwon-Zaleska 1
  • 1 Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland
  • 2 Department of Affective Disorders, Jagiellonian University Medical College, Cracow, Cracow, Poland
  • 3 Department of Psychiatry, Addiction Center, University of Michigan, Ann Arbor, MI 48109, USA, Ann Arbor, United States

The final, formatted version of the article will be published soon.

    Background: Due to its exceptional effectiveness, clozapine (CLO), whose metabolite is norclozapine (NCLO), is a drug of choice in the management of treatment-resistant schizophrenia. The purpose of this study was to assess the factors modifying the CLO/NCLO ratio (CNR). Methods: A total of 446 blood samples (233 of which were drawn from females and 213 from males, aged from 18 to 77 years) were analyzed in this study. The patients were treated at a psychiatric hospital in the period 2016-2021. Serum CLO and NCLO levels were determined with highperformance liquid chromatography coupled with a UV detector. Results: The median CNR was 2.38 (minimum 0.30, maximum 14.36). Our analysis showed that neither sex (p= 0.135) nor smoking (p=0.774) had any significant effect on the CNR. However, increased doses of CLO resulted in lower CNR values (p=0.005). Concomitant use of other psychotropic drugs increased the CNR (p=0.001).The results of our study indicate a need for personalized CLO treatment. Assessing the CNR may be useful in identifying CLO interaction with other psychotropic drugs.

    Keywords: Clozapine, Norclozapine, Clozapine-to-norclozapine ratio, clozapine metabolism, Schizophrenia

    Received: 28 Oct 2024; Accepted: 11 Dec 2024.

    Copyright: © 2024 Mach, Wnorowska, Siwek, Wojnar and Radziwon-Zaleska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Anna Wnorowska, Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.