Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients

Abstract

Objective

Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug–drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients.

Methods

In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM).

Results

Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40–70, and 70–100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40–60, and 60–100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40–53, and 53–100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40–100 kg schizophrenia patients, respectively.

Conclusion

Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.

Keywords:

• aripiprazole
• olanzapine
• population pharmacokinetics
• initial dosage optimization
• schizophrenia patients

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Cun Zhang, Lei Jiang, and Ke Hu are co-first authors for this study. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (No. 82104296), The Xuzhou Special Fund for Promoting Scientific and Technological Innovation (No. KC23217, No. KC23254), The Medical Research Project of Jiangsu Provincial Health Commission (No. Z2023010), The Initializing Fund of Xuzhou Medical University (No. RC20552111, No. RC20552222), The Fusion Innovation Project of Xuzhou Medical University (No. XYRHCX2021011, No. XYRHCX2022005), 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), Xuzhou Medical University Research Topic of Higher Education Teaching Reform (No. Xjyzrd202304).