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  • Title: Plasma and red blood cell concentrations of amiodarone during chronic therapy.
    Author: Heger JJ, Solow EB, Prystowsky EN, Zipes DP.
    Journal: Am J Cardiol; 1984 Mar 15; 53(7):912-7. PubMed ID: 6538381.
    Abstract:
    Amiodarone and a metabolite, desethylamiodarone, were measured in plasma of 55 patients and in both plasma and red blood cell (RBC) in 28 patients who received chronic amiodarone treatment. The assay for amiodarone and desethylamiodarone was performed by high-pressure liquid chromatography. During chronic treatment, median plasma concentration of amiodarone was 2.80 micrograms/ml and desethylamiodarone was 2.20 micrograms/ml. In matched samples, plasma amiodarone concentration exceeded RBC amiodarone concentration (p less than 0.001) and the RBC-to-plasma concentration ratio averaged 0.31. The plasma desethylamiodarone concentration was not significantly different from its RBC concentration, and the RBC-to-plasma concentration ratio averaged 1.29. There was a linear correlation between plasma concentrations of amiodarone and desethylamiodarone (r = 0.82) and between RBC concentrations of drug and metabolite (r = 0.71). Drug or metabolite concentrations in plasma and RBCs correlated directly with daily dosage of amiodarone. Adverse side effects during chronic amiodarone therapy were related most strongly to RBC drug and metabolite concentrations. The group with adverse side effects had a significantly higher RBC concentration of amiodarone, 150 vs 0.75 micrograms/ml (p less than 0.001), than did patients free of adverse effects. After dosage reduction, side effects abated and plasma and RBC concentrations of drug and metabolite decreased. These data indicate that there is an expected range of amiodarone and desethylamiodarone concentrations during chronic treatment and that adverse side effects correlate best with RBC concentrations of drug and metabolite. Red cell concentrations may reflect the amount of unbound, free amiodarone and desethylamiodarone in plasma.
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