Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the relationship between effect and dose/concentration

Abstract

Amiodarone is the most effective agent in the therapy of arrhythmias. However, the clinical effect of acute and chronic treatment is unclear and there are differences irrespective of comparable plasma/myocardial amiodarone and its metabolite desethylamiodarone concentations as well. Its unusual pharmacokinetics results in interindividual variation in plasma levels. The association between amiodarone and desethylamiodarone plasma levels and clinical efficacy is difficult to evaluate. This review was carried out to assess whether there is any objective correlation between amiodarone and desethylamiodarone plasma levels and the clinical effect. We summarized the results of relevant studies and clarified the relationship between plasma levels and effect vis á vis the pharmacokinetics and pharmacogenetics of this drug. Certain correlation was seen with oral amiodarone therapy, in others, plasma amiodarone levels were unrelated to therapeutic response and showed no correlation with changes in electrocardiogram or electrophysiological parametres. Several studies show that plasma concentration ranging between 0.5 and 2.5 mg/L appears to be the most effective, others demonstrate no difference between responders and non-responders. One way of interpreting plasma levels is to establish an individual patient´s effective concentration. Therapeutic drug monitoring can contribute to determining optimal concentration.

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction

“…This pulmonary deterioration may result in right heart failure. Finally, amiodarone possesses an unusually long and variable half‐life, which can range from 21 to 120 days It is extremely difficult, therefore, to gauge its compounded pharmacologic effects when used chronically.…”

“…Amiodarone is a class III antiarrhythmic drug that also has some properties of classes I, II, and IV antiarrhythmic drugs and has long been considered the antiarrhythmic drug of choice for ventricular tachyarrhythmias, especially in patients with end‐stage heart failure . The serum elimination half‐life of amiodarone has been found to range from 21 to 120 days . Adverse effects of amiodarone treatment are well‐documented, with gastrointestinal, neurologic, pulmonary, and thyroid toxicity among the most significant .…”

QTc prolongation and torsades de pointes due to a coadministration of fluoxetine and amiodarone in a patient with implantable cardioverter–defibrillator

“…The mechanism is also blockade of hERG encoded Ikr. [ 13 ] Drugs that block the Ikr channel increase the QTc interval and allow inward current, particularly calcium, to reactivate, leading to early after-depolarization in cardiac tissue. [ 13 ] In terms of pharmacokinetics, amiodarone has a large individual variation in systemic bioavailability.…”

“…[ 13 ] Drugs that block the Ikr channel increase the QTc interval and allow inward current, particularly calcium, to reactivate, leading to early after-depolarization in cardiac tissue. [ 13 ] In terms of pharmacokinetics, amiodarone has a large individual variation in systemic bioavailability. The highest concentrations of amiodarone were found in fat, liver, bone marrow, and lung tissue, which remained that concentrations of amiodarone were present in these tissues at several-fold higher than those in plasma.…”

“…In patients with impaired ventricular function, intravenous amiodarone increased the right ventricular effective refractory period and showed rate-dependent prolongation of the QTc interval. [ 13 ] Hence, the QTc interval is the more favorable indicator than the plasma concentration for predicting the cardiac toxicity. However, although amiodarone is known to prolong QTc interval, it rarely causes Tdp.…”