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Factors affecting drug concentrations and QT interval during thioridazine therapy

Lookup NU author(s): Dr Ruben ThanacoodyORCiD, Professor Ann DalyORCiD, Dr Joseph Reilly, Emeritus Professor Nicol Ferrier, Professor Simon ThomasORCiD

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Abstract

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.

Publication metadata

Author(s): Thanacoody RHK, Daly AK, Reilly JG, Ferrier IN, Thomas SHL

Publication type: Article

Publication status: Published

Journal: Clinical Pharmacology and Therapeutics

Year: 2007

Volume: 82

Issue: 5

Pages: 555-565

ISSN (print): 0009-9236

ISSN (electronic): 1532-6535

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.clpt.6100195

DOI: 10.1038/sj.clpt.6100195

PubMed id: 17460606

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