Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin oncardiac action potential duration

Fluoroquinolone antibiotics have been associated with QT prolongation follo wing administration to humans. This study compares the effects of four fluo roquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin e naction potential duration recorded from canine isolated cardiac Purkinje f ibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Actio n potential duration at 90% repolarization was recorded via intracellular m icroelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. M ean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2 +/- 0.7 mug/ml; grepafloxacin 9.3 +/- 0.9 mug/ml; moxifloxacin 9.9 +/- 1.6 mug/ml a nd ciprofloxacin 72.8 +/- 26.4 mug/ml. Prolongation was inverse frequency d ependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate tha t effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > cip rofloxacin. (C) 2000 Elsevier Science B.V. All rights reserved.