Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects.
BACKGROUND
Moxifloxacin is a new fluoroquinolone. In vitro studies have suggested that it could prolong ventricular repolarization. The main objective of this study was to measure the actual effect of single oral doses of moxifloxacin on QT interval duration in healthy volunteers.


METHODS
Nine men and 9 women participated in a double-blind, randomized, placebo-controlled, crossover study. Each participant received single oral doses (400 mg and 800 mg) of moxifloxacin or placebo. At the time of expected moxifloxacin maximum concentration, several electrocardiographic recordings were obtained at rest and during the course of a submaximal exercise test. QT interval and the corresponding RR interval value were measured within a wide range of RR intervals in each subject.


RESULTS
ANOVA showed that both moxifloxacin doses increased mean QT intervals compared with placebo. The mean QT interval duration at RR = 1000 ms was 379 +/- 24 ms during placebo, 394 +/- 33 ms during moxifloxacin 400 mg (P < .05), and 396 +/- 28 ms during moxifloxacin 800 mg (P < .05). Moxifloxacin-induced QT interval prolongation remained significant at all tested heart rates. The increase in QT interval duration relative to placebo remained between 2.3% +/- 2.8% and 4.5% + 3.8% across the range of RR intervals tested.


CONCLUSIONS
Moxifloxacin prolongs QT interval duration. The amplitude of this effect is small, and the risk of moxifloxacin-induced torsades de pointes is expected to be minimal when the drug is administered at the recommended dose of 400 mg/d. However, moxifloxacin should not be used in patients with predisposing factors of torsades de pointes such as electrolyte disturbances and bradycardia or during coadministration of proarrhythmic drugs.
Démolis
J L
JL
Department of Pharmacology, Saint-Antoine University Hospital, Paris, France.
Kubitza
D
D
Tennezé
L
L
Funck-Brentano
C
C
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D001372:Aza Compounds; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D024841:Fluoroquinolones; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077266:Moxifloxacin; D010919:Placebos; D011804:Quinolines; D016276:Ventricular Function / Q000187:drug effects* / Q000502:physiology
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D010919:Placebos; D011804:Quinolines; D000077266:Moxifloxacin