Amiodarone blood concentration in long-term therapy of paroxysmal atrial fibrillation: pharmacokinetic paradoxes and therapeutic drug monitoring (problem-based lecture)

Despite the rapid development of interventional treatment modalities and the introduction of novel antiarrhythmic drugs, amiodarone continues to occupy a unique niche in long-term relapse prevention therapy for atrial fibrillation. This is particularly relevant for patients with organic myocardial disease, chronic heart failure with reduced ejection fraction, and in regions with limited access to catheter ablation or costly alternative medications. However, the complex, multifactorial pharmacokinetics of amiodarone – high lipophilicity, enormous volume of distribution, the presence of the pharmacologically active metabolite desethylamiodarone, and an exceptionally long elimination half-life – pose significant challenges for clinicians. A narrow therapeutic window and a high risk of dose-dependent adverse effects justify the potential value of therapeutic drug monitoring (TDM). The lecture based on a critical appraisal of available evidence and real-world clinical data reviews current perspectives on the clinical significance of measuring amiodarone and desethylamiodarone concentrations. Pharmacokinetic features that determine patient management strategies are discussed in detail, along with the controversies surrounding existing clinical guidelines and the methodological limitations of published studies. Particular attention is devoted to identifying clinical scenarios in which TDM may be most informative and to outlining directions for future randomized controlled trials.