Key result
Hypertriglyceridemia linked to a ~50% higher amiodarone concentration-to-dose ratio due to increased lipoprotein binding.
Why the study?
Amiodarone and desethylamiodarone distribute to serum lipoproteins, prompting investigation into whether serum concentrations correlate with serum lipid levels and lipoprotein distribution in hyperlipidemia.
Does hypertriglyceridemia affect the serum concentration and distribution of amiodarone in patients treated for tachyarrhythmias?
Observational (n=116)
No
Does hypertriglyceridemia affect the serum concentration and distribution of amiodarone in patients treated for tachyarrhythmias?
Absolute Event Rate: 479% vs 320%
p-value: p=<0.001
Hypertriglyceridemia increases serum amiodarone concentrations through increased lipoprotein-binding and decreased metabolism, suggesting lipid levels may impact amiodarone pharmacokinetics.
May warrant lipid monitoring with amiodarone; hypothesis-generating for dose adjustments pending prospective studies.
Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very‐low‐density lipoprotein (VLDL) and low‐density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and DEA with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and DEA were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration‐to‐dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride ( r s = 0.541, p < 0.001) and was higher in the hypertriglyceridemic state than in normotriglyceridemic state (479 ± 211 vs. 320 ± 161, p < 0.001). No correlation was found between the C/D ratio of DEA and serum triglyceride levels ( r s = 0.272), although higher values were observed in the hypertriglyceridemic state (322 ± 125 vs. 285 ± 143, p < 0.001). In the hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction and decreased in high‐density lipoprotein and albumin fractions. The ratio of serum amiodarone to serum DEA, a metabolic ratio of amiodarone, positively correlated with serum triglyceride levels ( r s = 0.572, p < 0.001) and was higher in the hypertriglyceridemic state, suggesting that amiodarone metabolism decreased in hyperlipidemia. The results of this study reveal that serum concentrations of amiodarone increase in the hypertriglyceridemic state through the increased lipoprotein‐binding and decreased metabolism of amiodarone.
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Hashimoto et al. (2021) conducted an observational in Tachyarrhythmias (n=116). Amiodarone (Hypertriglyceridemic state) vs. Normotriglyceridemic state was evaluated on Concentration-to-dose (C/D) ratio of amiodarone (p=<0.001). Hypertriglyceridemia significantly increased the concentration-to-dose ratio of amiodarone compared to normotriglyceridemia (479 vs 320, p<0.001) due to increased lipoprotein-binding.
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