Amiodarone-associated changes in human neutrophils

Amiodarone and its major metabolite, desethylamiodarone, were measured in the plasma, white blood cells (WBCs) and red blood cells (RBCs) of 14 patients receiving chronic amiodarone therapy. The mean plasma concentrations (+/- standard error of the mean) of amiodarone and desethylamiodarone were 2.4 +/- 0.6 and 1.6 +/- 0.4 microgram/ml, respectively. The drug level in the WBCs was 62 +/- 12 micrograms/g protein during the early loading phase and 106 +/- 33 micrograms/g protein during maintenance phase of amiodarone therapy. Desethylamiodarone concentration in the WBCs was 42 +/- 18 and 190 +/- 33 micrograms/g protein during the loading and maintenance phases, respectively. Although a trend in WBC to plasma concentration was seen, there was no linear correlation between these levels. In 1 patient with severe neuropathy, biopsy of the nerve and muscle showed high concentrations of both amiodarone and desethylamiodarone. Although there was a decrease in tissue drug levels, proportionately high tissue:plasma drug levels were detected at the time of necropsy approximately 6.5 months after amiodarone was discontinued in this patient. Neutrophils from all patients receiving chronic amiodarone therapy showed multiple myelin-like polymorphic inclusion bodies (onionoid bodies) upon electron microscopic examination. Our observations suggest that WBC drug concentrations and electron microscopic changes may provide a means of correlating tissue concentrations and of following patients receiving chronic amiodarone therapy.