ArticleClinical and translational science2023
Impact of NFIB and CYP1A variants on clozapine serum concentration-A retrospective naturalistic cohort study on 526 patients with known smoking habits.
Article in Clinical and translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- ACKR1/Duffy-null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).British journal of clinical pharmacology · 2026Guideline
- Meta-analyses of clozapine, norclozapine levels and their ratio across three genome wide association studies.Translational psychiatry · 2025Pooled it
- 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
- Transcription factors of the Nuclear Factor I (NFI) family control hepatocyte differentiation and cytochrome P450 activity in human liver.Pharmacological research · 2025Article
- Impact of the transcription factor nuclear factor 1 B T>C polymorphism on clozapine metabolism in vivo and expression of intestinal transporters in vitro.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Impact ofTherapeutic advances in psychopharmacology · 2025Article
- Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo.European journal of clinical pharmacology · 2024Article
- How Real-World Data Can Facilitate the Development of Precision Medicine Treatment in Psychiatry.Biological psychiatry · 2024Review
- Genome-wide association analysis of treatment resistant schizophrenia for variant discovery and polygenic assessment.Human genomics · 2024Article
- Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.CNS drugs · 2024Article
- Rare variants in pharmacogenes influence clozapine metabolism in individuals with schizophrenia.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2024Article
- Impact of NFIB and CYP1A variants on clozapine serum concentration-A retrospective naturalistic cohort study on 526 patients with known smoking habits.Clinical and translational science · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical response of clozapine is closely associated with serum concentration. Although tobacco smoking is the key environmental factor underlying interindividual variability in clozapine metabolism, recent genome-wide studies suggest that CYP1A and NFIB genetic variants may also be of significant importance, but their quantitative impact is unclear. We investigated the effects of the rs2472297 C>T (CYP1A) and rs28379954 T>C (NFIB) polymorphisms on serum concentrations in smokers and nonsmokers. The study retrospectively included 526 patients with known smoking habits (63.7% smokers) from a therapeutic drug monitoring service in Norway. Clozapine dose-adjusted concentrations (C/D) and patient proportions with subtherapeutic levels (<1070 nmol/L) were compared between CYP1A/NFIB variant allele carriers and homozygous wild-type carriers (noncarriers), in both smokers and nonsmokers. Clozapine C/D was reduced in patients carrying CYP1A-T and NFIB-C variants versus noncarriers, both among smokers (-48%; p < 0.0001) and nonsmokers (-35%; p = 0.028). Patients who smoke carrying CYP1A-T and NFIB-C variants had a 66% reduction in clozapine C/D versus nonsmoking noncarriers (p < 0.0001). The patient proportion with subtherapeutic levels was 2.9-fold higher in patients who smoke carrying NFIB-C and CYP1A-T variants versus nonsmoking noncarriers (p < 0.0001). In conclusion, CYP1A and NFIB variants have significant and additive impact on clozapine dose requirements for reaching target serum concentrations. Patients who smoke carrying the studied CYP1A and NFIB variants, comprising 2.5% of the study population, may need threefold higher doses to prevent risk of clozapine undertreatment. The results suggest that pre-emptive genotyping of NFIB and CYP1A may be utilized to guide clozapine dosing and improve clinical outcomes in patients with treatment-resistant schizophrenia.
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