ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Schizophrenia
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1664678
Population pharmacokinetics modelling to predict DDI from zopiclone on clozapine in schizophrenia patients
Provisionally accepted
- 1The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China
- 2Xuzhou Medical University, Xuzhou, China
- 3Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
- 4Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, China
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Clozapine, as a core drug for the treatment of schizophrenia, is widely used in the drug treatment of schizophrenia patients. However, when multiple drugs are used in combination, it is not clear whether there are drug-drug interactions (DDI) of clozapine in patients with schizophrenia. This study aims to use population pharmacokinetics (PPK) modelling to predict DDI and individualized therapy of clozapine in schizophrenia patients. We collected 81 patients with schizophrenia and included their physiological data, biochemical data, treatment plans and information on combined medication during the clinical treatment process. Next, PPK modelling was used to analyze drugs with potential DDI when clozapine was used in schizophrenia patients, and dosage adjustments were recommended. Final analysis revealed that weight and coadministration of zopiclone affected clozapine clearance, and there was DDI with clozapine when zopiclone was used concurrently in schizophrenia patients. Further, for schizophrenia patients without zopiclone, 10 mg/kg/day, 9 mg/kg/day, 8 mg/kg/day and 7 mg/kg/day clozapine were recommended for 40-50 kg, 50-67 kg, 67-88 kg, and 88-120 kg patients, respectively. For schizophrenia patients with zopiclone, 6 mg/kg/day and 5 mg/kg/day clozapine were recommended for 40-70 kg and 70-120 kg patients, respectively. This study was the first to systematically analyze DDI when clozapine was used in schizophrenia patients and found DDI when zopiclone and clozapine were taken concurrently. Furthermore, when zopiclone was taken concurrently, clozapine dosage need to be reduced. Based on this, schizophrenia patients individualized dosage adjustment was recommended.
Keywords: population pharmacokinetics modelling, drug-drug interactions, individualized therapy, Clozapine, Schizophrenia
Received: 12 Jul 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Han, Zhang, Wang, Tian, Li, He, Zhang, Chen and Wang. 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:
Sumei He, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
Cun Zhang, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, China
Xiao Chen, Xuzhou Medical University, Xuzhou, China
Dongdong Wang, Xuzhou Medical University, Xuzhou, China
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