Correlation of the thickness of the left ventricular posterior wall (LVPWd) with various parameters, including age, gender, weight and height, was investigated in this study using regression models. Multicenter derived database comprised over 4,000 healthy individuals. The developed models were further utilized in the in vitro–in vivo (IVIV) translation of the drug cardiac safety data with use of the mathematical model of human cardiomyocytes operating at the virtual healthy population level. LVPWd was assumed to be equivalent to the length of one-dimensional string of virtual cardiomyocyte cells which was presented, as other physiological factors, to be a parameter influencing the simulated pseudo-ECG (pseudoelectrocardiogram), QTcF and Δ QTcF, both native and modified by exemplar drug (disopyramide) after IKr current disruption. Simulation results support positive correlation between the LVPWd and QTcF/Δ QTc. Developed models allow more detailed description of the virtual population and thus inter-individual variability influence on the drug cardiac safety.
Author(s): Kamil Fijorek, Felix Tanner, Barbara Stähli, Grzegorz Gielerak, Pawel Krzesinski, Beata Uzieblo-Zyczkowska, Pawel Smurzynski, Adam Stanczyk, Katarzyna Stolarz-Skrzypek, Kalina Kawecka-Jaszcz, Marek Jastrzebski, Mateusz Podolec, Grzegorz Kopec, Barbara Stanula, Maryla Kocowska, Zofia Tylutki, Sebastian Polak
Year: 2014 年 07 月 1 日