Effects of three fluoroquinolones on QT analysis after standard treatment courses.
BACKGROUND
Fluoroquinolone (FQ) agents have been speculated to influence the risk of Torsades de pointes (Tdp). Methods of evaluating this risk are varied and not systematic. QTc interval (QTc) prolongation is the most commonly used marker of Tdp, but has questionable utility. QT dispersion (QTd) may be a more selective marker of Tdp. No assessment of QTd for FQs has been reported. The current study evaluates the effects of three commonly prescribed FQs by comprehensive QT analysis.


METHODS
In an open-label crossover study, 13 healthy participants received 3 treatments in random order: ciprofloxacin 500 mg twice daily, levofloxacin 500 mg once daily, and moxifloxacin 400 mg once daily. Each treatment was given for 7 days with a 1-week washout period. Twelve-lead electrocardiographic measurements were performed prior to the first dose, 2 hours after the first dose, and following the 7-day medication course. QTc prolongation was determined by measurement of lead II, and QTd from the difference between the maximum and minimum QTc intervals among the 12 leads. The data were analyzed using Friedman ANOVA, with the Wilcoxon signed rank test post hoc analysis, with P < 0.05 significance.


CONCLUSIONS
No difference was seen in baseline QTc (P = 0.48) or QTd (P = 0.92). Following 7 days of moxifloxacin, the QTc was prolonged by 6 ms relative to baseline (408 ms, P = 0.022), and 11 ms from the 2-hour measurement (403 ms, P = 0.003). Ciprofloxacin and levofloxacin had no effect on QTc, and no FQ changed the QTd. Within our study population, ciprofloxacin and levofloxacin did not display an increased risk for Tdp. Moxifloxacin, while showing QTc prolongation, did not affect QTd, and an increased Tdp risk is questionable.
Tsikouris
James P
JP
University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA. jpt16@pitt.edu
Peeters
Michael J
MJ
Cox
Craig D
CD
Meyerrose
Gary E
GE
Seifert
Charles F
CF
D000704:Analysis of Variance; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D018709:Statistics, Nonparametric; D016171:Torsades de Pointes / Q000139:chemically induced*
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin