The influence of hyperlipoproteinemia on in vitro distribution of amiodarone and desethylamiodarone in human and rat plasma.

Purpose: To study the effect of hyperlipoproteinemia on in vitro distribution of amiodarone (AM) and its prevalent metabolite desethylamiodarone (DEA) in human and rat plasma.
Materials and Methods: Human and rat normolipidemic (NL) and hyperlipidemic (HL) plasma were spiked with AM and DEA. The fractions (high and low density lipoproteins, triglyceride rich lipoproteins and lipoprotein deficient plasma) were separated using ultracentrifugation.
Results: Human and rat displayed similar patterns in terms of association of AM and DEA in NL plasma, in which the highest and lowest associations were observed in lipoprotein deficient (LPDP) and triglyceride (TRL) rich plasma fractions, respectively. In HL a substantial shift was observed in partitioning of AM and DEA mostly to TRL. The shift of AM and DEA into TRL fraction of HL plasma was more drastic for rat than human. In HL, association of AM with rat LPDP and HDL fractions were 10 and 26-fold lower than in the corresponding human fractions, respectively. The DEA:AM ratio in rat, but not human, was significantly affected by HL.
Conclusion: HL caused a major shift of AM and DEA to TRL fraction in both species. The findings were consistent with the higher AM concentrations previously noted in HL rats given the drug.