NOEL GJ, ABELS R, MINTON N, NATARAJAN J, CHIEN S; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-639a.
RWJ Pharmaceutical Research Institute, Raritan, NJ.
BACKGROUND: Concern has been raised about the effect of FQs on ventricular repolarization because some FQs can influence rapid K+ channels and prolong QT interval in ECGs of laboratory animals. Levofloxacin (L), ciprofloxacin (C) and moxifloxacin (M) have been used widely and events associated with dysrhythmia have been reported rarely. Nevertheless, defining the potential for these FQs to affect ventricular repolarization is important because of their molecular relationship to other FQs (sparfloxacin, grepafloxacin) where a clinically significant effect on cardiac function has been strongly suggested. METHODS: Volunteers (n=48;18-84ys) were given single doses of L (1000mg), C (1500mg), M (800mg) and placebo (P) in a 4 period, double blind, randomized, cross-over study. A second similar design study (n=48;18-77yrs) was conducted using 500, 1000 and 1500mg single doses of L. QT intervals were measured manually at >7 defined times before and after dosing for each of the 4 periods and were corrected using Bazett's formula. The effect of treatment on mean post dose QTc, maximum change and change at Tmax was evaluated. RESULTS: The mean change in QTc post dose compared to baseline was -1.25, 3.88, 2.27 and 16.34 msec for P, L, C and M respectively. Differences in mean QTc change, maximum QTc change and QTc change at Tmax from baseline for L and C compared to M were significant (P<0.001). Differences between C and L were not significant. In the dose escalation trial with L, mean change in QTc from baseline was -0.69, 1.36, 2.81 and 6.89 msec for P, 500mg, 1000mg and 1500mg doses respectively. For mean QTc change from baseline, only the change for the 1500mg dose was significant from P. For mean QTc change at Tmax, differences were significant for 1000mg and 1500mg groups compared to P. CONCLUSIONS: QTc interval prolongation was evident and was significantly greater after a dose of M (800mg) than it was after a dose of either L (1000mg) or C (1500mg). Differences between L and C were not evident and mean change in QTc post dose for both of these drugs was <4msec. These results suggest that the influence of some FQs on QTc interval may be substantially greater than other FQs. The clinical relevance of these differences is not known.
Publication Types:
Keywords:
- Anti-Arrhythmia Agents
- Arrhythmias, Cardiac
- Aza Compounds
- Ciprofloxacin
- Double-Blind Method
- Electrocardiography
- Fluoroquinolones
- Ofloxacin
- Piperazines
- Quinolines
- grepafloxacin
- moxifloxacin
- sparfloxacin
Other ID:
UI: 102268518
From Meeting Abstracts