Optimization of initial dosage of quetiapine in schizophrenic patients: effects of fluvoxamine or duloxetine coadministration

Front Pharmacol. 2024 Nov 20:15:1496043. doi: 10.3389/fphar.2024.1496043. eCollection 2024.

Abstract

Objective: Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug-drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).

Methods: Ninety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs.

Results: It was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40-50 and 50-120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40-120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40-120 kg range.

Conclusion: The present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine.

Keywords: drug–drug interactions; duloxetine; fluvoxamine; optimal initial dosage; quetiapine; schizophrenic patient.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. The present study was supported by the Xuzhou Special Fund for Promoting Scientific and Technological Innovation (Nos KC23217 and KC23254), The Medical Research Project of Jiangsu Provincial Health Commission (No. Z2023010), Jiangsu Province Education Science Planning Project (No. C/2022/01/36), Xuzhou Medical University Labor Education Special Project (No. X1d202209), Jiangsu Province Higher Education Informatization Research Topic (No. 2023JSETKT136), and Xuzhou Medical University Research Topic of Higher Education Teaching Reform (No. Xjyzrd202304).