Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers.
1. Sparfloxacin, a new fluoroquinolone, slightly increases the duration of the QT interval. Reverse rate-dependence of QT interval prolongation has been shown for many agents that are known to prolong QT interval duration, and QT prolongation at slow heart rates may be a risk factor for torsades de pointes. 2. A double-blind, randomized, placebo controlled, crossover study was performed in 15 healthy volunteers to determine the effects of single oral doses of sparfloxacin (200 and 400 mg) on the QT interval at various heart rates. 3. 12-lead ECGs were recorded at rest and during exercise tests 5 h after sparfloxacin or placebo administration. QT intervals were calculated at predetermined RR intervals (1000, 800, 700, 600, 500 and 400 ms) after individual QT-RR curve fitting. 4. Sparfloxacin at both doses induced prolongation of the QT interval which was around 4% greater than placebo. No significant reverse rate-dependence of QT interval prolongation was observed. 5. Oral administration of sparfloxacin appears unlikely to be associated with marked QT interval prolongation.
Demolis
J L
JL
Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France.
Charransol
A
A
Funck-Brentano
C
C
Jaillon
P
P
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D016276:Ventricular Function / Q000187:drug effects*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C061363:sparfloxacin