The Effects of Moxifloxacin on QTc Interval in Healthy Korean Male Subjects

Abstract

Background and objectiveMoxifloxacin 400 mg is a widely used positive control in thorough QT (TQT) studies, but its QT-prolonging effects in Korean subjects have not been studied. The present study was conducted to collect pilot data in Korean subjects after moxifloxacin administration to evaluate the adequacy of moxifloxacin as a positive control.MethodsThirty-eight, healthy, Korean, male subjects were recruited for pharmacokinetic (PK) blood sampling and electrocardiography (ECG) recordings at three different study sites. On day 1, a baseline 12-lead ECG was recorded, and on day 2, ECG recordings were conducted after placebo, or moxifloxacin 400- or 800-mg administration. Baseline-corrected, placebo-adjusted, corrected QT (ΔΔQTc) values were calculated. Blood samples were collected after moxifloxacin administration and PK parameters were assessed.ResultsA total of 33 subjects completed the study. The largest time-matched ΔΔQTc occurred approximately 4 h after dosing, with ΔΔQTcI (QT interval corrected by individual QT-RR regression model) values of 11.66 ms (moxifloxacin 400 mg) and 20.96 ms (800 mg). The mean and 90 % confidence intervals of ΔΔQTcI did not include zero at any of the measurement time points. There was a positive correlation between plasma moxifloxacin concentration and ΔΔQTcI (r = 0.422). Dose-proportional PK profiles were observed.ConclusionMoxifloxacin 400 mg is an adequate positive control in Korean TQT studies. Our results indicate that moxifloxacin 400 mg can be used to evaluate the cardiac safety of a drug in Korean subjects.

Moxifloxacin‐induced QTc interval prolongations in healthy male Japanese and Caucasian volunteers: a direct comparison in a thorough QT study

“…The QT c effect of moxifloxacin observed in our study is also consistent with available data from other welldesigned QT studies in selected ethnic groups, which also suggest lack of significant ethnic sensitivity to the QT-prolonging effect of moxifloxacin [22][23][24][25][26]. In a TQT study of telbivudine in 53 subjects, all of whom were Hispanics, the ΔΔQT c F for moxifloxacin was lower at 10.0 (90% CI 6.9, 13.1) ms [23].…”

“…In a TQT study of telbivudine in 53 subjects, all of whom were Hispanics, the ΔΔQT c F for moxifloxacin was lower at 10.0 (90% CI 6.9, 13.1) ms . A prospective study of two doses (400 mg and 800 mg) of moxifloxacin effect in only the Korean population also reported that its QT effect in that population was comparable with its known effect in Caucasians with concentration vs. ΔΔQT c F response slope of 5.35 ms per µg ml –1 . Sugiyama et al .…”

QTc Interval Prolongation in Drug Resistant-Tuberculosis Patients Treated with Shorter Treatment Regimen

“…Moxifloxacin 400 mg is known to cause a mean increase in the QTc interval of between 10 and 14 ms in 2-4 hours after a single oral dose. In addition, a supratherapeutic dose of moxifloxacin (800 mg) results in a nearly two-times increase in the QTc interval from baseline compared with the 400-mg dose (22) . Unfortunately, this study did not mention 600 mg dose.…”

Pharmacokinetic-pharmacodynamic analysis to evaluate the effect of moxifloxacin on QT interval prolongation in healthy Korean male subjects

“…The results of this TQT study describing baseline-corrected, placebo-adjusted differences in ΔQTc (ΔΔQTc) caused by moxifloxacin dose has been reported previously. 22 …”