A method for studying tricyclic antidepressant cardiotoxicity in relation to their kinetics in the rabbit

Elizabetta Dejana, R. Latini, Laura Preziati, A. Quintana, Aurora Bonaccorsi

Research output: Contribution to journalArticlepeer-review

Abstract

An investigation was conducted to study whether animals with experimental cardiovascular disorders were more sensitive to the cardiotoxic effects of nortriptyline (NT) than normal animals. Since increased toxicity might be due to hypersensitivity of the target organ (the heart) and/or to increased blood levels of the drug, NT blood levels and an electrocardiogram (ECG) were simultaneously recorded in unanesthetized rabbits during NT intravenous infusion. Nortriptyline induced marked ECG alterations such as tachycardia, arrhythmias, impaired conduction, ST and T wave abnormalities, although only the increase in PQ and QRS intervals were directly correlated with NT blood levels (p <0.01). A one-compartment model described the pharmacokinetics and pharmacodynamics of NT disappearance. Nortriptyline blood levels of about 0.5 μg ml caused a 10% increase in PQ and QRS. A 20% complex widening occurred at 1 μg ml. The pharmacokinetics and cardiac effects of NT did not significantly differ in rabbits with experimental myocardial infarction (isoprenaline 50 mg kg × 2 days), hyperthyroid rabbits (triiodothyronine 0.1 mg kg × 15 days), or controls.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalJournal of Pharmacological Methods
Volume2
Issue number3
DOIs
Publication statusPublished - 1979

Keywords

  • Cardiotoxicity
  • Nortriptyline
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology

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