An observation on QT variability in healthy male volunteers

A retrospective analysis was performed on 12‐lead ECGs obtained from 110 healthy male subjects. The purpose of this study was to investigate and observe the variation of QTc throughout a 24‐hour period. Data was obtained from subjects who received placebo on Phase I studies. For consistency the same ECG timepoints relative to dosing were selected for analysis (0, 1, 2, 4, 8, 12 and 24h post dose). All ECGs were obtained using the Marquette MAC5000 machine. QT intervals and heart rates were measured automatically and the QT/RR relationship was modelled using Bazett's formula. The mean QTcB interval at each timepoint varies between 374.7ms and 380.3ms. The range in QTcB value is very high with a large standard deviation. The lowest and highest values observed for QTcB were 219ms and 425ms respectively. The data presented shows that various factors need to be considered when designing studies to detect a significant effect on QT interval. Care is required in the selection of appropriate ECG baseline measurements and choice of correction formula used. Baseline values from a single ECG should not be used. Multiple baseline ECGs will give a better indication of an individual's mean QTc value. However, serial ECGs taken at similar times to the treatment day will minimise any effects of diurnal variation. Although Bazett's is widely used it may be that Fridericia's or individualised formulae are more appropriate for a given population. Clinical Pharmacology & Therapeutics (2004) 75 , P8–P8; doi: 10.1016/j.clpt.2003.11.028