Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin on cardiac action potential duration.
Fluoroquinolone antibiotics have been associated with QT prolongation following administration to humans. This study compares the effects of four fluoroquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on action potential duration recorded from canine isolated cardiac Purkinje fibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Action potential duration at 90% repolarization was recorded via intracellular microelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. Mean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2+/-0.7 microg/ml; grepafloxacin 9.3+/-0.9 microg/ml; moxifloxacin 9.9+/-1.6 microg/ml and ciprofloxacin 72.8+/-26.4 microg/ml. Prolongation was inverse frequency dependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate that effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > ciprofloxacin.
Patmore
L
L
Department of Pharmacology, Quintiles Scotland Ltd., Research Park, Heriot Watt University, Riccarton, EH14 4AP, Edinburgh, UK. leslie.patmore@quintiles.com
Fraser
S
S
Mair
D
D
Templeton
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002939:Ciprofloxacin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D024841:Fluoroquinolones; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D000077266:Moxifloxacin; D010879:Piperazines / Q000494:pharmacology*; D011804:Quinolines; D013997:Time Factors
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D010879:Piperazines; D011804:Quinolines; D002939:Ciprofloxacin; C075375:grepafloxacin; C061363:sparfloxacin; D000077266:Moxifloxacin