Dose-dependent effects of oral dronedarone on the circadian variation of RR and QT intervals in healthy subjects: implications for antiarrhythmic actions.
Dronedarone, a non-iodinated benzofuran derivative, was developed as a potentially less toxic alternative to amiodarone. This study describes Holter data of dronedarone in humans. Five groups of healthy subjects were given 1 of 5 oral doses of dronedarone in a twice-daily regimen or placebo. Holter recordings of circadian rhythmicity of RR and QT intervals were evaluated. Dronedarone prolonged RR and QT intervals as a function of dose, without effect on circadian patterns. The relative prolongation of QT, QTc, and RR by dronedarone was significant. The QTc interval did not exhibit a clearly recognizable circadian pattern, suggesting that the circadian pattern of the QT interval was mostly a reflection of circadian changes in the RR interval in the study population. Dronedarone resembled amiodarone in class III and sympatholytic effects, indicating its potential as a unique antiarrhythmic compound seemingly devoid of the side effects mediated by iodine in amiodarone.
Wadhani
Nitin
N
David Geffen School of Medicine at University of California, Los Angeles, USA.
Sarma
Jonnalagedda Sm
JS
Singh
Bramah N
BN
Radzik
David
D
Gaud
Christine
C
D000284:Administration, Oral; D000328:Adult; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000077764:Dronedarone; D015716:Electrocardiography, Ambulatory; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D012016:Reference Values
D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone