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.
Highlights
Amiodarone is the most effective antiarrhythmic medications available today for the treatment of both atrial and ventricular arrhythmias
The relatively poor bioavailability is probably mediated by intestinal wall metabolism via CYP3A4 in addition to gastrointestinal excretion mediated by P-glycoprotein
DEA inhibits the activities of both CYP3A4 and P-glycoprotein, it is suggested that the bioavailability of amiodarone is gradually increased over time in patients receiving longterm amiodarone therapy[4]
Summary
Amiodarone is the most effective antiarrhythmic medications available today for the treatment of both atrial and ventricular arrhythmias. It was shown that the range of amiodarone concentration was wide after rapid intravenous administration. The elevation of DEA concentrations lagged behind the change in amiodarone concentrations, which were below clinically effective levels. This discrepancy presumably reflects slow biotransformation of the parent drug[5]. CYP3A4 which constitutes 30% of the total CYP content in human liver is expected to be the major isoform involved in amiodarone metabolism. The ratio of DEA to amiodarone remained relatively constant over different dosage or drug concentration ranges, but increased with duration of treatment (reaching approximately 80% than of amiodarone after several months), suggesting a timedependent metabolic function[11].
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