title: Effects of three fluoroquinolones on QT interval in healthy adults after single doses.
abstract: OBJECTIVE
  A clinical trial was conducted in healthy adult volunteers to assess the effect of levofloxacin, moxifloxacin, and ciprofloxacin on the QT and QTc interval.
  
  
  METHODS
  Electrocardiograms were recorded 24 hours before and after subjects took placebo, 1000 mg levofloxacin, 800 mg moxifloxacin, and 1500 mg ciprofloxacin in a double-blind, randomized, 4-period, 4-treatment, 4-sequence crossover trial. Changes in QT and QTc interval from baseline were assessed by several different methods.
  
  
  RESULTS
  Increases in QT and QTc interval compared with placebo were consistently greater after moxifloxacin compared with either levofloxacin or ciprofloxacin. The mean postdose change from baseline QTc (Bazett) intervals for the 24-hour period after treatment with moxifloxacin ranged from 16.34 to 17.83 ms (P < .001, compared with placebo). For levofloxacin, this change ranged from 3.53 to 4.88 ms (P < .05, compared with placebo), and for ciprofloxacin, this change ranged from 2.27 to 4.93 ms (P < .05, compared with placebo, with the use of 3 of 5 baseline methods).
  
  
  CONCLUSIONS
  A change in QTc (Bazett) interval from baseline can be demonstrated safely in healthy volunteers after single high doses of fluoroquinolones that achieve approximately 1.5 times the maximum plasma drug concentration that occurs after recommended doses. There is substantial daily variation in both QT and QTc interval, and the magnitude and frequency of changes in QTc interval can depend on the methods used. These factors need to be considered because clinical trials measuring the effects of drugs on QT intervals are used to estimate the risk of using these drugs. Greater changes in QT and QTc intervals after treatment with moxifloxacin compared with levofloxacin or ciprofloxacin are consistent with in vitro observations related to the effect of these drugs on rapid potassium (IK(r)) channels. The clinical relevance of these differences is not known.
authors.affiliation: Johnson &Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ 08869, USA. gnoel1@prius.jnj.com
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Noel
authors.forename: Jaya
authors.initials: J
authors.lastname: Natarajan
authors.forename: Shuchean
authors.initials: S
authors.lastname: Chien
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hunt
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Goodman
authors.forename: Robert
authors.initials: R
authors.lastname: Abels
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001372:Aza Compounds; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D011804:Quinolines
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin