Lookup NU author(s): Dr Ruben Thanacoody,
Professor Ann Daly,
Dr Joseph Reilly,
Professor Nicol Ferrier,
Professor Simon Thomas
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The objective of this study was to investigate factors affecting steady-state plasma concentrations of thioridazine. A cross-sectional study of patients receiving chronic thioridazine was employed. Common allelic variants of CYP2D6 and CYP2C19, as well as thioridazine and metabolite concentrations and QTc intervals, were determined. In 97 patients, dose-corrected plasma concentrations (C/Ds) of thioridazine and metabolites were correlated with age but not sex or CYP2C19 genotype. Patients with no functional CYP2D6 alleles (n=9) had significantly higher C/D for thioridazine (P=0.017) and the ring sulfoxide metabolite and a significantly higher thioridazine/mesoridazine ratio compared with those with ≥1 functional CYP2D6 allele (n=82). Smokers had significantly lower C/D for thioridazine, mesoridazine, and sulforidazine and significantly lower thioridazine/ring sulfoxide ratios than non-smokers. QTc interval was not significantly affected by CYP2D6 or CYP2C19 genotypes. Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP2D6 genotype does not appear to influence on-treatment QTc interval.
Author(s): Thanacoody RHK, Daly AK, Reilly JG, Ferrier IN, Thomas SHL
Publication type: Article
Publication status: Published
Journal: Clinical Pharmacology and Therapeutics
ISSN (print): 0009-9236
ISSN (electronic): 1532-6535
Publisher: Nature Publishing Group
PubMed id: 17460606
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