Amiodarone and N-desethylamiodarone concentrations in plasma, red blood cells, and myocardium after a single oral dose: relation to hemodynamic effects in surgical patients.

In an attempt to assess their respective values for purposes of drug monitoring, plasma, red blood cell, atrial, and ventricular concentrations of amiodarone and N-desethylamiodarone (NDA) were measured, in 50 surgical patients, after a single oral dose (30 mg/kg); hemodynamic changes were assessed also. Amiodarone concentration was lower in red blood cells than in plasma and in myocardium. A relationship was found between the red blood cell concentration and plasma or myocardial concentrations of amiodarone (r = 0.79 and r = 0.68, p less than 0.00001). Hemodynamic studies were available in 17 treated patients and 13 control subjects before and at the time of surgery. In control subjects, hemodynamics did not change with time and general anesthesia. Oral amiodarone decreased the cardiac index (p less than 0.05) and heart rate (p less than 0.001) without significant changes in arterial pressure, systemic vascular resistance, or stroke volume index. The increase in capillary wedge pressure was related to amiodarone or NDA plasma, myocardial, and red blood cell concentrations (for amiodarone: r = 0.61, p = 0.006; r = 0.69, p less than 0.001; and r = 0.53, p = 0.02, respectively). We concluded that oral amiodarone impairs hemodynamics and that measurement of the amiodarone plasma concentration rather than the red blood cell concentration is the easiest method of monitoring the drug. However, establishment of the clinical utility of drug monitoring during chronic administration of amiodarone needs further investigation.