Evidence map›Paper›PMID 41262335›Full record

ArticleDrug design, development and therapy2025

Clozapine Drug-Drug Interactions and Individualized Dosing in Bipolar Disorder: A Model-Informed Precision Dosing Approach.

Yue Zhang, Jie Wang, Xue Tian, Yi-Jia Zhang, Ye Li, Su-Mei He, Cun Zhang, Xiao Chen, Dong-Dong Wang

Abstract read
In one paragraph

Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yue Zhang *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Jie Wang *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Xue Tian *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Yi-Jia Zhang *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Ye Li *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Su-Mei HeDepartment of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, People's Republic of China.
Cun ZhangDepartment of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Xiao ChenSchool of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.
Dong-Dong WangJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy and School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.ORCID 0000-0002-4019-5530

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Clozapine is an effective treatment for bipolar disorder (BD), but its clinical use is complicated by drug-drug interactions (DDI), which may reduce efficacy or increase toxicity. This study aims to explore clozapine DDI and its individualized administration regimens for patients with BD based on model-informed precision dosing (MIPD) technology, and achieve clinical precision medication. Methods: Data are collected from 51 patients with BD treated with clozapine, including all concomitant medications used in clinical practice. The MIPD technique is used to explore the potential DDI, and the Monte Carlo simulation is adopted to recommend the optimal administration regimen. Results: It is ultimately found that zopiclone, zolpidem tartrate with clozapine have DDI. When patients with BD have no combined medication of zopiclone or zolpidem tartrate, the recommended doses of clozapine for patients at 40-45 kg, 45-60 kg, 60-78 kg, 78-106 kg, and 106-120 kg are 10 mg/kg/day, 9 mg/kg/day, 8 mg/kg/day, 7 mg/kg/day, and 6 mg/kg/day, respectively. When patients with BD are combined with zopiclone, the recommended doses of clozapine for patients at 40-60 kg and 60-120 kg are 4 mg/kg/day and 3 mg/kg/day, respectively. When patients with BD are combined with zolpidem tartrate, the recommended doses of clozapine for patients at 40-52 kg and 52-120 kg are 5 mg/kg/day and 4 mg/kg/day, respectively. Conclusion: This study explores the DDI of clozapine in patients with BD based on MIPD, and recommends the individualized dosing regimen of clozapine in patients with BD according to concomitant medication. These findings provide weight- and drug-specific dosing recommendations that may improve the safety and efficacy of clozapine in BD patients.

Indexed as

Antipsychotic AgentsBipolar DisorderClozapineAdultAzabicyclo CompoundsDose-Response Relationship, DrugDrug InteractionsFemaleHumansMaleMiddle AgedMonte Carlo MethodPiperazinesPrecision MedicineZolpidemAntipsychotic AgentsAzabicyclo CompoundsClozapinePiperazinesZolpidemzopiclonebipolar disorderclozapinedrug–drug interactionszolpidem tartratezopiclone

Identifiers

PMID41262335
PMCPMC12626042

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.