RELATION BETWEEN AMIODARONE AND DESETHYLAMIODARONE PLASMA-CONCENTRATIONS AND ELECTROPHYSIOLOGIC EFFECTS, EFFICACY AND TOXICITY

[摘要] Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients receiving amiodarone. The early electrophysiologic effects of amiodarone were assessed in 40 consecutive patients with coronary artery disease and sustained ventricular tachycardia or fibrillation who underwent electrophysiologic studies and measurement of amiodarone plasma concentration before and 29 .+-. 15 (mean .+-. SD) days after initiation of therapy. Amiodarone and desethylamiodarone plasma levels did not correlate with changes in either sinus cycle length, QTc interval, ventricular effective refractory period, AH and HV intervals or ventricular tachycardia cycle length. Amiodarone and desethylamiodarone plasma concentrations and the effects of the drug on conduction intervals or right ventricular effective refractory periods were not related to suppression of arrhythmia induction by ventricular stimulation after 1 month of therapy. The relation between amiodarone plasma concentrations and both toxicity and efficacy during long-term therapy were prospectively assessed in a larger series of 114 consecutive patients with either symptomatic supraventricular or ventricular arrhythmias who were followed up on long-term amiodarone therapy for 26 .+-. 15 months. Sixty-three patients (55%) had one or more adverse effects attributed to amiodarone. By life-table analysis, 40, 69 and 80% of patients had experienced an adverse reaction after 1, 2 and 3 years of therapy, respectively. Elevated hepatic enzymes (34%), subclinical hypothyroidism (18%) and skin discoloration (13%) were the most common adverse reactions observed. Elevation of hepatic enzyme activities was related to higher mean daily dose and plasma concentrations of amiodarone whereas skin discoloration was related to accumulated dose, but substantial overlap between doses and levels in patients with and without toxicity made the clinical utility of these findings small. Hypothyroidism occurred with similar frequency at all doses and plasma concentrations. Amiodarone plasma concentrations also did not differ between the 85 effectively and 29 ineffectively treated patients. These data indicate that monitoring amiodarone or desethylamiodarone levels is of limited clinical value for assessing electrophysiologic effects or for predicting significant clinical toxicity during therapy with doses between 100 and 400 mg/day.

[发布日期] 1987-05-01