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Electrocardiographic QTc Changes Due to Moxifloxacin Infusion

From St. Paul's Cardiac Electrophysiology, London, England (Dr Malik, Dr Hnatkova); St. George's, University of London, London, England (Dr Malik, Dr Hnatkova); and Wilhelminenspital der Stadt Wien, Vienna, Austria (Dr Schmidt, Dr Smetana).

Moxifloxacin (400-mg single dose) is a frequent positive control in thorough QT/QTc studies. This investigation assessed baseline and placebo-controlled QTc changes (QTc, individualized correction for heart rate and rate hysteresis) at 126 data points before, during, and after 1-hour moxifloxacin infusion in 44 healthy participants and in their sex-, race-, and age-defined subgroups. Constant linear QTc increase was found during the infusion. The postinfusion peak QTc values (corresponding to maximum plasma levels) were not statistically different in women (16.1 ± 6.5 ms) and men (15.1 ± 5.3 ms), Africans (15.3 ± 5.3 ms) and whites (15.6 ± 6.6 ms), and participants younger (16.5 ± 4.8 ms) and older (14.7 ± 6.6 ms) than the median age of 35 years. The QTc values were different in participants with a body mass index (BMI) below (16.8 ± 5.4 ms) and above 30 kg/m² (10.8 ± 5.1 ms; P = .008). Although the population mean QTc changes closely followed mean plasma-level kinetics (4.8 ms per 1 µg/mL), the individual postinfusion peak QTc was not related to individual peak plasma levels (P = NS) but was strongly related to BMI (P = .0007). Thus, the individual pharmacokinetic/pharmacodynamic effects are substantially variable; obese participants should be excluded from thorough QT/QTc studies.

Key Words: QTc prolongation • assay sensitivity • moxifloxacin infusion

Address for reprints: Marek Malik, PhD, MD, St. Paul's Cardiac Electrophysiology, London, 16 Verulam Avenue, Purley, Surrey CR8 3NQ, England; e-mail: marek.malik{at}btinternet.com.

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