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

• Autorzy: Tylutki Z. , Jornil J. , Polak S.

Identyfikatory

DOI

10.1515/bams-2015-0043

• Języki publikacji: EN

Abstrakty

EN

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 APD90) increase with drug concentrations. APD90 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.

Słowa kluczowe

EN

drug safety; modeling; simulation

• Wydawca: Uniwersytet Jagielloński - Collegium Medicum ; Index Copernicus Sp. z o.o.
• Czasopismo: Bio-Algorithms and Med-Systems
• Rocznik: 2016
• Tom: Vol. 12, no. 1
• Strony: 33--38
• Opis fizyczny: Bibliogr. 22 poz., rys., tab.

Twórcy

autor

Tylutki Z.

• Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Social Pharmacy, Jagiellonian University Medical College, Medyczna 9 Str. Cracow 30-688, Poland

autor

Jornil J.

• Department of Forensic Medicine, Aarhus University, Aarhus, Denmark

autor

Polak S.

• Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Social Pharmacy, Jagiellonian University Medical College, Krakow, Poland

Bibliografia

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Uwagi

Opracowanie ze środków MNiSW w ramach umowy 812/P-DUN/2016 na działalność upowszechniającą naukę.