Clinical electrophysiologic effects of a single high oral dose of amiodarone

Abstract

Several recent reports have described the antiarrhythmic effects of a single high oral dose of amiodarone but clinical electrophysiologic effects have not been reported. The present study was performed to assess electrophysiologic effects in 12 patients. After baseline electrophysiologic studies (EPS) patients were administered a single oral dose of 30 mg/kg of amiodarone. EPS was repeated 7.5 +/- 0.5 hours later. Plasma levels of amiodarone and its metabolite desethylamiodarone were determined at the time of the second EPS, Holter monitoring was performed for 24 hours after amiodarone administration. Amiodarone significantly increased the following parameters: corrected QT interval (+4.5%), functional refractory period of the right atrium (+7%); AH interval (+12.3%), effective refractory period of the atrioventricular node (+18.5%), and cycle length of Wenckebach block (+8.4%). These effects were not correlated with plasma levels of amiodarone and desethylamiodarone. Holter monitoring detected no significant bradycardia or arrhythmia. These findings indicate that the effects of a single high oral dose of amiodarone are the same as those known to be induced by acute intravenous administration.

QT interval prolongation by noncardiovascular drugs: A proposed assessment strategy

“…Bretylium and amiodarone have also been categorized as class III agents. Amiodarone has a pronounced effect on the QT interval but seldom causes TDP [Keren et al, 1982;Bhandari et al, 1984;Deharo et al, 1997]. Bepridil is an example of another drug which prolongs the QT interval but does not cause TDP [Leclercq et al, 1983;Funck-Brentano et al, 1990;Lecocq et al, 1990].…”

Benefit-risk evaluation of olanzapine, risperidone and sertindole in the treatment of schizophrenia

“…The results of animal studies (Ben-David and Zipes 1990) suggest that, at a given QT c interval, the ␣ 1 -antagonistic effect of sertindole, together with the slight tachycardia it causes, reduces the risk of bradycardia which can develop into torsades de pointes. The protective effects of ␣ 1 -receptor blockade have also been shown to be of clinical relevance (Deharo et al 1997).…”

Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients with Atrial Tachyarrhythmias

“…It is theoretically conceivable that including plasma concentrations of amiodarone and N-desethylamiodarone could have improved our predictions. It is however unlikely since individual plasma concentrations are poorly predictive of pharmacodynamics response [40,41] .…”

“…Total number of amiodarone administrations 361 154 (3) -0.23 (41) 0.85 (27) 0.67 (18) 0.86 (29) 154 bpm (3) . 131 bpm (4) 103 bpm (20) 132 bpm (26) 0.14 (11) (20) 136 bpm (29) 1.42 (13) 0.8 (11) (31) 0.37 (31) 0.26 (46) Residual variability, bpm 16 (2) Abbreviations: AT = Atrial fibrillation; Amio 50 = Amiodarone dosage that induces 50% of putative maximal effect on HR reduction; DOBU = beta-agonist administration; bpm = beats per minute; BSV = between-subject variability; ECV : electrical cardio-version; FILL = fluid therapy; FRetro HR = factor determining the importance of endogenous spontaneous retrocontrol of the HR to a reference HR depending on the type of cardiac rhythm at the time of first administration of amiodarone in ICU; HR 0 = heart rate at t 0 before first amiodarone dosing in ICU; ICU = intensive care unit; KDE = rate constant describing the equilibrium between the administration rate and the observed effect, k out = first-order constant rate for Amio effect kinetics; %rse = percent relative standard error; NA = not applicable; MG = magnesium loading; Parox = Paroxystic atrial tachyarrhythmia which started less than one FIGURE 1…”