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Effect of sodium valproate on aripiprazole pharmacokinetics and initial dosage optimization in bipolar disorder
Su-Mei He, Chang-Xiao Zhang, Ying-Wei Jin, Lei Jiang, Cun Zhang, Yi-Guo Jiang, Dong-Dong Wang
Su-Mei He, Yi-Guo Jiang, Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215153, Jiangsu Province, China
Chang-Xiao Zhang, Department of Geriatrics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Ying-Wei Jin, Department of Pharmacy, The Suqian Clinical College of Xuzhou Medical University, Suqian 223800, Jiangsu Province, China
Lei Jiang, Dong-Dong Wang, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
Cun Zhang, Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
Co-first authors: Su-Mei He and Chang-Xiao Zhang.
Co-corresponding authors: Yi-Guo Jiang and Dong-Dong Wang.
Author contributions: He SM and Zhang CX analyzed the data and drafted the manuscript, and they made equal contributions to this work as co-first authors; He SM, Zhang CX, Jin YW, Jiang L, Zhang C, Jiang YG, and Wang DD performed the research, contributed to data interpretation, and revised the manuscript; Jiang YG and Wang DD designed the study, and they contributed equally to this work as co-corresponding authors. All authors approved the final version to publish.
Supported by Suzhou Applied Basic Research Science and Technology Innovation Project, No. SYWD2024258; Basic Science (Natural Science) Project of Higher Education Institutions in Jiangsu Province, No. 25KJD310004; Jiangsu Province Higher Education Informatization Research Project, No. 2023JSETKT136; Xuzhou Medical University Research Project on Reform of Postgraduate Education and Teaching, No. XYJGKT202506; and Xuzhou Medical University Teaching Academic Research Project, No. 2024ZDKT02-Y03.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, No. 20220725011.
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data used in this study can be available from the corresponding author upon request.
Corresponding author: Dong-Dong Wang, PhD, Adjunct Professor, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou 221004, Jiangsu Province, China.
13852029591@163.com
Received: February 14, 2026
Revised: March 21, 2026
Accepted: April 15, 2026
Published online: August 19, 2026
Processing time: 154 Days and 2.7 Hours
BACKGROUND
Aripiprazole provides clinical benefits in patients with bipolar disorder (BD).
AIM
To explore drug-drug interactions and optimize the initial dosage of aripiprazole in patients with BD.
METHODS
Patients with BD treated with aripiprazole were retrospectively analyzed. A virtual clinical trial approach was applied, with a population pharmacokinetic model developed using non-linear mixed effects modeling.
RESULTS
Weight and coadministration of sodium valproate sustained-release tablets were identified as significant factors influencing aripiprazole clearance. Aripiprazole clearance increased by 66.7% in patients receiving sodium valproate sustained-release tablets. For patients weighing 40-120 kg without sodium valproate, the optimal initial dosage was 0.3 mg/kg, and for those receiving sodium valproate, the optimal initial dosage was 0.4 mg/kg.
CONCLUSION
This study explored drug-drug interactions and initial dosage optimization of aripiprazole in patients with BD using a virtual clinical trial approach. Coadministration of sodium valproate sustained-release tablets increases aripiprazole clearance in patients with BD, indicating that a higher initial dosage of aripiprazole may be required.
Core Tip: This study aims to explore drug-drug interactions and initial dosage optimization of aripiprazole in patients with bipolar disorder (BD). Aripiprazole clearance rate increases 66.7% in patients with BD taking sodium valproate sustained-release tablet. The present study explores the drug-drug interactions and initial dosage optimization of aripiprazole in patients with BD based on virtual clinical trial for the first time. When sodium valproate sustained-release tablet is used in combination, the clearance of aripiprazole in patients with BD is accelerated, and the dosage of aripiprazole in patients with BD need to be increased.
