Aims: To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects.
Methods: Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas. Concentrations were measured by liquid chromatography-tandem mass spectrometry.
Results: Plasma levels of amiodarone and N-desethyl-amiodarone were significantly correlated with daily maintenance doses (R= 0.52, P= 0.003). Amiodarone concentrations in fat tissue were four to 226 times (mean 55) higher than in plasma, and well correlated with plasma levels (R= 0.68, P < 0.001). Concentrations of amiodarone and N-desethyl-amiodarone in adipose tissue did not significantly increase with higher total cumulated doses or longer treatment duration. Nine of 12 patients who had received amiodarone for > or =2 years developed clinically important adverse effects, predominantly hypothyroidism (n= 6), compared with two of 18 patients treated for less time (relative risk 6.75; 95% confidence interval 1.8, 26). The incidence of those adverse effects was not significantly associated with amiodarone concentrations, whether in plasma or in adipose tissue.
Conclusions: We found no evidence of excessive or unexpected accumulation of amiodarone in fat tissue on long-term administration. Late amiodarone adverse effects, particularly hypothyroidism, are associated with longer exposure times, but do not seem to be explained by higher concentrations in plasma or in fat tissue.