The apparent partition coefficient (P) of amiodarone between aqueous buffer and lipid vesicles or erythrocyte ghosts was determined by equilibrium distribution using [125I]amiodarone as a tracer. The lipid vesicles consisted of total lipids extracted from erythrocyte or of egg phosphatidylcholine alone or mixed with a varying amount of stearic acid, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, or cholesterol. All the conditions yielded a similar value of P (P approximately equal to 17,000). The log value of the partition coefficient of the neutral form of the drug is log PN = 5.95. The value of the extrapolated 1-octanol-buffer partition coefficient is log PN,oct = 6.66. Partition coefficient measurements on erythrocyte ghosts suggested that amiodarone partitioned to a similar extent in the protein and lipid content of the membrane.
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