Trial reportEuropean journal of clinical pharmacology2003
Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.
Trial report in European journal of clinical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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
16 citing papers in PubMed, 52 citations in OpenAlex.
- No effect of the CYP1A2*1F genotype on thioridazine, mesoridazine, sulforidazine plasma concentrations in psychiatric patients.European journal of clinical pharmacology · 2007Trial
- Precision Medicine into Clinical Practice: A Web-Based Tool Enables Real-Time Pharmacogenetic Assessment of Tailored Treatments in Psychiatric Disorders.Journal of personalized medicine · 2021Article
- Thioridazine Is an Efflux Pump Inhibitor in Mycobacterium avium Complex but of Limited Clinical Relevance.Antimicrobial agents and chemotherapy · 2020Article
- A phase 1 trial evaluating thioridazine in combination with cytarabine in patients with acute myeloid leukemia.Blood advances · 2018Article
- Clinical applications of CYP genotyping in psychiatry.Journal of neural transmission (Vienna, Austria : 1996) · 2015Review
- Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.Pharmacogenomics and personalized medicine · 2014Review
- Personalized medicine: is it a pharmacogenetic mirage?British journal of clinical pharmacology · 2012Review
- Quantitative prediction of cytochrome P450 (CYP) 2D6-mediated drug interactions.Clinical pharmacokinetics · 2011Article
- Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2.The AAPS journal · 2009Review
- Genetic polymorphism of glutathione S-transferase T1 (GSTT1) and QT-interval in schizophrenia patients.Journal of molecular neuroscience : MN · 2009Article
- Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.Clinical pharmacokinetics · 2009Article
- Cytochrome P450 2D6 genotyping: potential role in improving treatment outcomes in psychiatric disorders.CNS drugs · 2009Article
- Low frequency of CYP2D6 poor metabolizers among schizophrenia patients.The pharmacogenomics journal · 2007Article
- Thioridazine: resurrection as an antimicrobial agent?British journal of clinical pharmacology · 2007Review
- Isoniazid bactericidal activity and resistance emergence: integrating pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic populations.Antimicrobial agents and chemotherapy · 2007Article
- Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response.Molecular psychiatry · 2004Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 7% of Caucasians have genetically impaired activity of the cytochrome P450 enzyme CYP2D6 and are classified as poor metabolizers (PM). The disposition of thioridazine has been related to the CYP2D6 phenotype. The present study aimed to evaluate the influence of CYP2D6 and CYP2C9 genotypes, and tobacco smoking on steady-state thioridazine plasma levels.
methodsSeventy-six Caucasian psychiatric patients receiving thioridazine monotherapy were studied. Debrisoquine metabolic ratio (MR) and steady-state plasma levels of thioridazine and its metabolites, mesoridazine and sulforidazine, as well as CYP2D6 (in 74 patients) and CYP2C9 (in 63 patients) genotypes were determined.
resultsThe median dose-corrected, steady-state plasma concentrations (C/D) of thioridazine were related to the number of functional CYP2D6 alleles ( P<0.01), being 15.2, 7.2, 4.0, 4.2 nmol/l per milligram in subjects with no, one, two, and three or more functional CYP2D6 genes, respectively. No significant differences were found in the C/Ds of mesoridazine or sulforidazine. No relationship was found between CYP2C9 genotype and plasma levels of thioridazine or its metabolites. The median C/D of thioridazine was significantly ( P<0.001) lower in smokers (4.0 nmol/l per milligram, range: 1.0-15.5; n=58) than in nonsmokers (7.4 nmol/l per milligram, range: 2.8-23.6; n=18). Also, the C/Ds of mesoridazine and sulforidazine were lower in smokers ( P<0.01). The plasma thioridazine/mesoridazine ratio significantly correlated with the debrisoquine MR ( r(2)=0.30, P<0.001).
conclusionThe results show that the plasma concentrations of thioridazine and its metabolites are influenced by tobacco smoking and the CYP2D6 genotype, and support the dose-dependent inhibition of CYP2D6 by thioridazine. CYP2C9 does not play an important role in thioridazine metabolism.
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