Binding of amiodarone by serum proteins and the effects of drugs, hormones and other interacting ligands

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Abstract
Amiodarone is chiefly bound to albumin (62·1%) and much of the remainder (33·5%) is carried on a high molecular weight protein, probably β-lipoprotein. Analysis of data for amiodarone binding to albumin revealed a high affinity primary binding site (Ka 5·6 times 106 litre mol−1) with about four secondary sites (average Ka 1·9 times 105 litre mol−1). Studies of the binding of amiodarone in serum revealed one type of binding site only with an affinity constant (Ka 4·2 times 106 litre mol−1) similar to that of the primary site on albumin. The secondary albumin binding sites do not seem therefore to be utilized in whole serum and the affinity of the lipoprotein must be similar to that of the primary amiodarone binding site on albumin. The effects of a wide range of compounds on albumin binding of amiodarone were examined by equilibrium dialysis. Quinidine, amitriptyline, cephazolin and palmitate decreased albumin-bound [125I]amiodarone. Neither warfarin nor digoxin affected the binding of amiodarone by albumin, thus of the three drugs known to be potentiated by concomitant amiodarone administration, only potentiation of quinidine could be explained by displacement from serum albumin. Rifampicin, frusemide, phenytoin, (-)-adrenaline, bromocresol green, (-)-noradrenaline and bromocresol purple were found to increase binding of [125I]amiodarone by albumin. Amiodarone had no influence on the distribution of iodothyronines amongst their binding proteins nor were the concentration or binding properties of these proteins altered after prolonged treatment with the drug. Thus altered iodothyronine concentrations in amiodarone-treated patients cannot be attributed even in part to effects at the serum binding protein level.