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Bio-Algorithms and Med-Systems

Editor-in-Chief: Roterman-Konieczna , Irena

CiteScore 2017: 0.43

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The effect of increasing amitriptyline doses on cardiomyocytes’ electrophysiology – simulation study

Zofia Tylutki
  • Corresponding author
  • Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Social Pharmacy, Jagiellonian University Medical College, Krakow, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jakob Jornil / Sebastian Polak
  • Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Social Pharmacy, Jagiellonian University Medical College, Krakow, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-02-12 | DOI: https://doi.org/10.1515/bams-2015-0043


Background: Overdoses of tricyclic antidepressants may lead to arrhythmia. The aim of the study was to simulate the effect of increasing concentrations of amitriptyline (AMI) and its metabolite, nortriptyline, on the action potential of human ventricular cell.

Methods: Simulations were performed in Cardiac Safety Simulator platform with the use of the O’Hara-Rudy model. Input data included literature-derived, drug-specific IC50 values for ICa(L), IKr, and INa currents. Individual concentrations of AMI and nortriptyline were simulated in Simcyp. Nine single doses (mg) were tested: 5, 10, 50, 100, 300, 500, 1000, 5000, and 10,000.

Results: The values of simulated endpoints (APD50, APD90, triangulation, and ΔAPD90) increase with drug concentrations. ΔAPD90 was statistically significant for doses up from 1000 mg. EADs were observed after administration of 10,000-mg AMI.

Conclusions: The consequences of various doses of AMI on the single cardiac myocytes were simulated in our study. Repolarization abnormalities were not expected for the therapeutic doses. EADs may be observed for very high doses of AMI.

Keywords: drug safety; modeling; simulation


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About the article

Corresponding author: Zofia Tylutki, Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Social Pharmacy, Jagiellonian University Medical College, Medyczna 9 Str. Cracow 30-688, Poland, E-mail:

Received: 2015-11-27

Accepted: 2015-12-14

Published Online: 2016-02-12

Published in Print: 2016-03-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Project was financed by the National Science Centre, Poland, project number 2014/13/N/NZ7/00254.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Bio-Algorithms and Med-Systems, Volume 12, Issue 1, Pages 33–38, ISSN (Online) 1896-530X, ISSN (Print) 1895-9091, DOI: https://doi.org/10.1515/bams-2015-0043.

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