ArticleThe pharmacogenomics journal2020
Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity.
Article in The pharmacogenomics journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pharmacokinetic Markers of Clinical Outcomes in Severe Mental Illness: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Population Pharmacokinetics of Clozapine: A Systematic Review.BioMed research international · 2020Pooled it
- Factors Influencing Phenoconversion in CYP-Mediated Drug Metabolism: A Scoping Review.Pharmacy (Basel, Switzerland) · 2026Review
- CYP2D6 Genotypes Do Not Affect Clozapine Levels in a Large, Multicenter Cohort: Time Has Come to Revise Food and Drug Administration's Clozapine Packet Insert.Schizophrenia bulletin · 2026Article
- Factors affecting voriconazole pharmacokinetic variability in critically ill patients: a systematic review.Critical care (London, England) · 2026Article
- A Call to Action for Starting Clozapine: Increasing Clozapine Use and Safety in a Post-REMS Era.Focus (American Psychiatric Publishing) · 2025Review
- Following the Action of Atypical Antipsychotic Clozapine and Possible Prediction of Treatment Response in Schizophrenia.Life (Basel, Switzerland) · 2025Review
- Impact ofTherapeutic advances in psychopharmacology · 2025Article
- Effect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2024Article
- Review
- The potential influence of estrogen-containing oral contraception on clozapine metabolism in a patient with known pharmacogenomic status.The mental health clinician · 2024Article
- Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.European archives of psychiatry and clinical neuroscience · 2024Article
- CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.Scientific reports · 2023Article
- Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count.Schizophrenia (Heidelberg, Germany) · 2023Article
- Effect of CYP2D6 pharmacogenetic phenotype and phenoconversion on serum concentrations of antidepressants and antipsychotics: a retrospective cohort study.International journal of clinical pharmacy · 2023Article
- Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders: The Functional Role of CYP2D6 and CYP2C19.Journal of personalized medicine · 2023Article
- Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach.Journal of personalized medicine · 2023Article
- Delineating gene-environment effects using virtual twins of patients treated with clozapine.CPT: pharmacometrics & systems pharmacology · 2023Article
- Categorization of Cytochrome P4502D6 Activity Score by Urinary Amphetamine/Methamphetamine Ratios.Metabolites · 2022Article
- Pharmacogenomics in Psychiatry Practice: The Value and the Challenges.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clozapine is an atypical antipsychotic metabolized by CYP1A2, CYP2D6, and CYP2C19 enzymes. Among 66 adult schizophrenia patients treated with clozapine-based combination therapies, we explored the impact of genotype-predicted CYP1A2, CYP2D6, and CYP2C19 activity on dose-adjusted clozapine concentrations and symptom severity, with and without correction for inhibitors and inducers of these enzymes. Uncorrected activity scores were not associated with dose-adjusted clozapine concentrations or symptom severity. CYP1A2 and CYP2D6 activity scores corrected for known inducers (i.e., smoking) and inhibitors (e.g., concomitant medications) were associated with dose-adjusted clozapine levels and in the case of CYP1A2, symptom severity. However, smoking status and certain inhibitors of clozapine metabolism (i.e., esomeprazole) explained significantly more variance in dose-adjusted clozapine levels relative to corrected activity scores. These findings highlight the clinical importance of nongenetic factors (smoking, concomitant medications) and suggest that the added utility of CYP1A2, CYP2D6, and CYP2C19 activity scores to guide clozapine dosing is currently limited.
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Registered trials
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