QTc interval prolongation by fexofenadine in healthy human volunteers and its correlation with plasma levels of fexofenadine: A demonstration of anticlockwise hysteresis.

Aim: The study was designed to establish relationship between the plasma concentration and QTc interval prolonging effect of fexofenadine and demonstrate the phenomenon of anticlockwise hysteresis.

Materials And Methods: Six subjects were given fexofenadine 60 mg tablet orally under stable conditions, and their drug concentrations were measured at regular intervals. At predetermined time, their ECGs were recorded. Data were analyzed and plotted graphically.

Design And Setting: Randomized parallel design, single group study conducted at clinical research organization of Ahmadabad.

Results: In all subjects time taken for maximum plasma concentration of fexofenadine (T(max)) was around 3 h and the value of average maximum plasma concentration was 460.63 ng/mL, the effect of fexofenadine on the heart (measured as QTc interval prolongation) was maximum (E(max)) after 6 h and average QTc interval was 469.75 ms. Thus, the time to maximum concentration of fexofenadine did not match with the maximum effect on the heart as measured by QTc interval.

Conclusion: The relationship between the drug concentration and drug effect on the heart are at two different time scales. It can be understood by two-compartment model of pharmacokinetics, and this retardation or lagging of an effect behind the concentration is known as hysteresis. The increase of QTc was not beyond 500 ms and not sustained, demonstrating overall cardiac safety of fexofenadine.