QTc interval lengthening is related to CYP2D6 hydroxylation capacity and plasma concentration of thioridazine in patients

Adrián LLerena, R. Berecz, Alfredo De la Rubia, Pedro Dorado

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Thioridazine cardiotoxicity has been associated with a prolonged heart-rate corrected QT (QTc) interval. However, no systematic studies have been performed on patients at therapeutic doses. The present study aimed to evaluate the influence of dose and plasma concentration of thioridazine and CYP2D6 enzyme status on the QTc interval in psychiatric patients. Sixty-five Spanish European psychiatric patients receiving thioridazine antipsychotic monotherapy were studied. The plasma levels of thioridazine and its metabolites were determined by high-performance liquid chromatography. All patients were phenotyped for CYP2D6 activity with debrisoquine during treatment. Thirty-five patients (54%) had a QTc interval over 420 ms. The lengthening of QTc interval was correlated with plasma concentration (p <0.05) and daily dose (p <0.05) of thioridazine. CYP2D6 enzyme hydroxylation capacity, evaluated by debrisoquine metabolic ratio (MR) (p <0.05) and thioridazine/mesoridazine ratio (p <0.05), was also correlated with QTc intervals. The present study shows the relationship between QTc interval lengthening among psychiatric patients treated at therapeutical doses with the dose and the plasma concentration of thioridazine. Since debrisoquine MR has been shown to be correlated with the QTc intervals, CYP2D6 enzyme hydroxylation capacity might be relevant in determining the risk for QTc interval lengthening. Patients with impaired CYP2D6 enzyme activity due to enzyme inhibition by thioridazine might be more prone to increased risk of sudden death due to torsade de pointes type cardiac dysrhythmia.

Original languageEnglish
Pages (from-to)361-364
Number of pages4
JournalJournal of Psychopharmacology
Volume16
Issue number4
Publication statusPublished - Dec 2002

Fingerprint

Thioridazine
Cytochrome P-450 CYP2D6
Hydroxylation
Debrisoquin
Psychiatry
Enzymes
Mesoridazine
Torsades de Pointes
Sudden Death
Antipsychotic Agents
Cardiac Arrhythmias
Heart Rate
High Pressure Liquid Chromatography

Keywords

  • CYP2D6
  • Debrisoquine
  • QTc lengthening
  • Thioridazine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)

Cite this

QTc interval lengthening is related to CYP2D6 hydroxylation capacity and plasma concentration of thioridazine in patients. / LLerena, Adrián; Berecz, R.; De la Rubia, Alfredo; Dorado, Pedro.

In: Journal of Psychopharmacology, Vol. 16, No. 4, 12.2002, p. 361-364.

Research output: Contribution to journalArticle

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