Electrocardiographic QTc changes due to moxifloxacin infusion.

Moxifloxacin (400-mg single dose) is a frequent positive control in thorough QT/QTc studies. This investigation assessed baseline and placebo-controlled QTc changes (DeltaDeltaQTc, 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 DeltaDeltaQTc increase was found during the infusion. The postinfusion peak DeltaDeltaQTc 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 DeltaDeltaQTc values were different in participants with a body mass index (BMI) below (16.8 +/- 5.4 ms) and above 30 kg/m(2) (10.8 +/- 5.1 ms; P = .008). Although the population mean DeltaDeltaQTc changes closely followed mean plasma-level kinetics (4.8 ms per 1 microg/mL), the individual postinfusion peak DeltaDeltaQTc 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.

RCT Entities:   Population Interventions Outcomes