Comparison of the Effects of Thioridazine and Mesoridazine on the QT Interval in Healthy Adults After Single Oral Doses

We compared the effects of single doses of thioridazine and mesoridazine on the heart rate‐corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochlori...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2007-11, Vol.82 (5), p.548-554
Main Authors: Salih, I S M, Thanacoody, R H K, McKay, G A, Thomas, S H L
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - adverse effects
Antipsychotic Agents - blood
Antipsychotic Agents - pharmacokinetics
Area Under Curve
Biological and medical sciences
Cross-Over Studies
Dopamine Antagonists - administration & dosage
Dopamine Antagonists - adverse effects
Dopamine Antagonists - blood
Dopamine Antagonists - pharmacokinetics
Double-Blind Method
Electrocardiography
Female
Heart Conduction System - drug effects
Humans
Long QT Syndrome - chemically induced
Long QT Syndrome - physiopathology
Male
Medical sciences
Mesoridazine - administration & dosage
Mesoridazine - adverse effects
Mesoridazine - blood
Mesoridazine - pharmacokinetics
Middle Aged
Pharmacology. Drug treatments
Reference Values
Thioridazine - administration & dosage
Thioridazine - adverse effects
Thioridazine - blood
Thioridazine - pharmacokinetics
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Summary:We compared the effects of single doses of thioridazine and mesoridazine on the heart rate‐corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double‐blind, crossover study. Mean maximum increases in the QTc interval following thioridazine (37.3±4.1 ms, P=0.023) and mesoridazine (46.6±7.4 ms, P=0.021) were similar and significantly greater than following placebo (12.9±8.1 ms). The area under the effect–time curve over 8 h following drug administration was similar between the two drugs (129.3±22.1 vs 148.3±43.0 ms h). In conclusion, thioridazine and mesoridazine are associated with similar effects on the QTc interval. Clinical Pharmacology & Therapeutics (2007) 82, 548–554; doi:10.1038/sj.clpt.6100194; published online 4 April 2007
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100194