Effects of moxifloxacin on QT interval in conscious dogs.
Moxifloxacin has been shown to induce QT prolongation in both clinical and preclinical models. However, the ability to observe this effect at clinically relevant concentration in normal conscious dogs has not been reported. The purpose of this study was to investigate the effects of moxifloxacin on the QT interval in conscious, healthy dogs. Four male mongrel dogs were chronically instrumented for the measurement of arterial blood pressure, left ventricular blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature. Animals were administered a 1-h i.v. infusion of moxifloxacin once per day via a catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50 mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and QTc prolongation was observed. A statistically significant prolongation in the QT interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma concentrations. This study demonstrate that a study design with four dogs was sensitive enough to measure moxifloxacin-induced QT prolongation at clinically relevant plasma concentrations.
Mittelstadt
S W
SW
Procter & Gamble Pharmaceuticals, Miami Valley Laboratories, Cincinnati, OH 45252, USA. mittelstadt.sw@pg.com
Hart
S M
SM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D024841:Fluoroquinolones; D006329:Heart Conduction System / Q000187:drug effects*; D007262:Infusions, Intravenous / Q000662:veterinary; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012016:Reference Values
D000889:Anti-Arrhythmia Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin