Therapeutic monitoring of amiodarone and desethylamiodarone after surgical ablation of atrial fibrillation-evaluation of the relationship between clinical effect and the serum concentration

Abstract

Background Association between clinical effect and serum concentration of amiodarone (AMI) and its active metabolite desethylamidarone (DEA) in patients after surgical ablation (SA) of atrial fibrillation (AF) has not yet been studied. Aims We wanted to find a correlation between AMI and DEA serum concentration and maintaining sinus rhythm (SR) after SA of AF. Methods Sixty eight patients with AF who had undergone surgical ablation between 2014 and 2017 were included in a single-centre, prospective, observational study. Maintaining of SR was evaluated by standard 12-lead ECG and 24-hour Holter ECG monitoring at months 1, 3, 6 and 12 following surgery. Therapeutic monitoring of AMI and DEA concentrations was done to optimize therapy and adverse effects were followed up. Results We have noticed a high success rate in maintaining of SR (overall 83%). The median of serum concentration of AMI was 0.81 mg/L (range 0.16–2.35 mg/L) and DEA 0.70 mg/l (range 0.19–2.63 mg/L). No significant differences were found in the serum concentratration of AMI, DEA or DEA/AMI concentratration ratios between patients with SR and persistent supraventricular tachyarrhythmia except on the second outpatient visit. We observed significant correlation between serum concentration of DEA and thyroid-stimulating hormone elevation. Conclusion We confirmed the efficacy of AMI and DEA at the measured serum concentrations. However, analysis of these concentrations alone cannot replace assessment of the clinical response for treatment. Establishment of individual AMI (and DEA) concentrations at which the optimal therapeutic response is achieved seems to be advantageous. Therapeutic monitoring of AMI and DEA is helpful in personalised pharmacotherapy after SA of AF.

Use of Therapeutic Drug Monitoring in Amiodarone Treatment: A Systematic Review of Recent Literature

“…Table 1 summarizes the characteristics of the 19 included articles. In the clinical setting, blood concentrations were used with the intention of performing dose adjustments (ie, TDM) in 5 studies, [9][10][11][12][13] although only 3 studies reported a change in amiodarone treatment. [10][11][12] From these 3 published studies, only the case report by Munnink et al used TDM to modify the amiodarone dose during rifampicin treatment, whereas the 2 case reports by Kim et al and Sato et al discontinued amiodarone treatment due to side effects and toxicity.…”

“…3 For dosage modifications, 5 clinical studies used blood amiodarone concentration measurements. 9–13 Amiodarone concentration measurements were used to adjust amiodarone medication 1–12 months after surgical ablation in a prospective observational study of 68 patients with atrial fibrillation. 9 There were no statistical differences in doses or concentrations of amiodarone or MDEA between individuals with maintained sinus rhythm and those with tachyarrhythmias, and both sinus rhythm and tachycardia were detected within the complete concentration range (0.11–2.5 mcg/mL).…”

“…Eleven articles used TDM for clinical purposes, such as dose adjustment, 9 toxicity, side effects, 11–13,15–18 or drug–drug interactions 10,19,20 ; 6 articles used TDM for pharmacokinetic purposes, 14,21–25 and 2 articles used TDM for other effects of amiodarone, such as lipoprotein 26 and cholesterol metabolism. 3 For dosage modifications, 5 clinical studies used blood amiodarone concentration measurements.…”

“…9–13 Amiodarone concentration measurements were used to adjust amiodarone medication 1–12 months after surgical ablation in a prospective observational study of 68 patients with atrial fibrillation. 9 There were no statistical differences in doses or concentrations of amiodarone or MDEA between individuals with maintained sinus rhythm and those with tachyarrhythmias, and both sinus rhythm and tachycardia were detected within the complete concentration range (0.11–2.5 mcg/mL). Regardless of the concentration measurements, amiodarone dosages were increased if tachycardia was detected on electrocardiograms, resulting in doses ranging from 143 to 1200 mg/d throughout a 12-month follow-up period.…”

“…Regardless of the concentration measurements, amiodarone dosages were increased if tachycardia was detected on electrocardiograms, resulting in doses ranging from 143 to 1200 mg/d throughout a 12-month follow-up period. 9 Given the number of amiodarone blood tests performed in the daily clinic, it is noteworthy that these concentrations did not result in changes in amiodarone therapy because the effect was monitored by electrocardiograms. Others have found that TDM/blood concentrations cannot substitute the assessment of the clinical response evaluation based on symptoms and electrocardiograms.…”