ArticleThe international journal of neuropsychopharmacology2017
Potential Role of Patients' CYP3A-Status in Clozapine Pharmacokinetics.
Article in The international journal of neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Population Pharmacokinetics of Clozapine: A Systematic Review.BioMed research international · 2020Pooled it
- A scoping review of genetic studies of treatment-resistant schizophrenia.Frontiers in genetics · 2026Review
- Influence of pharmacokinetics-related gene polymorphisms on plasma levels of clozapine and its metabolites in Japanese patients with schizophrenia.PCN reports : psychiatry and clinical neurosciences · 2025Article
- Impact ofTherapeutic advances in psychopharmacology · 2025Article
- Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine.Frontiers in psychiatry · 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
- Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder.Journal of psychopharmacology (Oxford, England) · 2024Article
- The potential influence of estrogen-containing oral contraception on clozapine metabolism in a patient with known pharmacogenomic status.The mental health clinician · 2024Article
- Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction.Frontiers in psychiatry · 2024Article
- The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions.Psychiatry and clinical psychopharmacology · 2023Article
- Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia.Therapeutic advances in psychopharmacology · 2023Review
- Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Experience with comprehensive pharmacogenomic multi-gene panel in clinical practice: a retrospective single-center study.Croatian medical journal · 2022Article
- Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.Translational psychiatry · 2022Article
- Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives.Frontiers in pharmacology · 2022Review
- Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation.Clinical pharmacokinetics · 2021Article
- Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2021Article
- Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia.Scientific reports · 2020Article
- End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s.Pharmacological reports : PR · 2020Article
- Clinical Pharmacokinetics of Atypical Antipsychotics: An Update.Clinical pharmacokinetics · 2018Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since a potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients. Results: The patients' CYP2C19 or CYP2D6 genotypes and CYP1A2 expression seemed to have no effect on clozapine serum concentration, whereas CYP3A4 expression significantly influenced the normalized clozapine concentration (185.53±56.53 in low expressers vs 78.05±29.57 or 66.52±0.25 (ng/mL)/(mg/kg) in normal or high expressers, P<.0001), in particular that the patients expressed CYP1A2 at a relatively low level. The functional CYP3A5*1 allele seemed to influence clozapine concentrations in those patients who expressed CYP3A4 at low levels. The dose requirement for the therapeutic concentration of clozapine was substantially lower in low CYP3A4 expresser patients than in normal/high expressers (2.18±0.64 vs 4.98±1.40 mg/kg, P<.0001). Furthermore, significantly higher plasma concentration ratios of norclozapine/clozapine and clozapine N-oxide/clozapine were observed in the patients displaying normal/high CYP3A4 expression than in the low expressers. Conclusion: Prospective assaying of CYP3A-status (CYP3A4 expression, CYP3A5 genotype) may better identify the patients with higher risk of inefficiency or adverse reactions and may facilitate the improvement of personalized clozapine therapy; however, further clinical studies are required to prove the benefit of CYP3A testing for patients under clozapine therapy.
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