ArticleJournal of psychopharmacology (Oxford, England)2024
Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder.
Article in Journal of psychopharmacology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Clozapine and anti-cancer agents: a systematic literature review of case reports.CNS spectrums · 2025Pooled it
- C-Reactive Protein and Neutrophil-To-Lymphocyte Ratio: Can They Be Used Interchangeably in Tracking Clozapine-Related Inflammation?Pharmacotherapy · 2026Article
- Clozapine-Induced Gastrointestinal Hypoperfusion Leading to Bowel Ischemia and Secondary Atrial Fibrillation: A Case Report.Case reports in psychiatry · 2026Article
- A Case of Clozapine Toxicity Caused by Infection in a Patient with Treatment-Resistant Schizophrenia.International medical case reports journal · 2026Article
- Clozapine Drug-Drug Interactions and Individualized Dosing in Bipolar Disorder: A Model-Informed Precision Dosing Approach.Drug design, development and therapy · 2025Article
- Population pharmacokinetics modelling to predict DDI from zopiclone on clozapine in schizophrenia patients.Frontiers in psychiatry · 2025Article
- Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I: A Review of the Pharmacokinetic Literature and Proposed Changes.Journal of clinical psychopharmacologyReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is high inter-individual variability in clozapine metabolism due to genetic and non-genetic differences. Patient-specific factors such as smoking, inflammation indicated by elevated C-reactive protein (CRP), and certain concurrent medications have a significant influence on clozapine metabolism.
aimTo assess which patient-specific factors best explain variability in clozapine metabolism estimated by clozapine concentration to dose (C/D) ratios.
methodsA retrospective cohort analysis using electronic medical data was conducted on 172 inpatients at the BC Psychosis Program. Patients with normal renal and liver function were included if they were on clozapine and had at least one steady-state plasma concentration. The degree of influence of each factor on the variability of clozapine metabolism in the entire cohort and subgroups stratified by fluvoxamine use was evaluated using multiple linear regression analysis of C/D ratios.
resultsModel fit testing showed that the entire cohort model accounts for 52.7% of C/D ratio variability, while the no fluvoxamine and fluvoxamine models accounted for 40.8% and 43.8%. In the entire cohort (
conclusionIn a clinical population, this study replicated the relationship between reduced rate of clozapine metabolism and the use of fluvoxamine, elevated CRP, obesity, nonsmoking status, and female sex; and the magnitude of the effects were large enough to be clinically relevant.
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