Plasma Levels Of Amiodarone Research Articles

Effects of amiodarone administration during lactation in Fischer-344 rats

The antiarrhythmic drug, amiodarone, was administered (35 mg/kg, p.o.) once daily to lactating Fischer-344 rats for either the first 7 days of lactation, the first 14 days of lactation, or for the full 24-day lactational period. Treatment with amiodarone resulted in a decrease in maternal weight gain compared to pair-fed vehicle-treated controls, however, neonatal weight gain was not affected. The concentration of amiodarone in the maternal milk was approx. 6-fold higher than its primary metabolite, desethylamiodarone. Plasma levels of amiodarone and desethylamiodarone were higher in maternal rats compared to neonates. Both amiodarone and desethylamiodarone were distributed to neonatal tissues through lactational transfer. The levels of desethylamiodarone were higher in neonatal lung compared to liver at all treatment times. They were also elevated above amiodarone in neonatal lung at all treatment times. The amiodarone levels in neonatal lung and liver were similar.

Rapid Microdetermination of Amiodarone and its Metabolite N. Desethylamiodarone in Plasma by High-Performance Liquid Chromatography

Abstract A rapid microdetermination of amiodarone (A) and its metabolite, N. Desethylamiodarone (DA) in plasma by HPLC is described. 100μL of plasma are deproteinized by 200μL of acetonitrile containing triflupromazine as an internal standard. After centrifugation, 20pL of supernatant aliquot are injected into a Nucleosil octyl analytical column and eluted with a mixture of acetonitrile, 0.01 M sodium acetate pH 3.3 and triethylamine (84 : 16 : 0.1 v/v) at a flow rate of 2.0 mumin. Detection limit is 50 ng/mL for both compounds. Between run CVs range from 2.5 to 4.2%. No interference is observed either with endogenous substances or with a variety of drugs frequently used in cardiovascular therapy. This simple procedure is suitable for routine determination of plasma levels of amiodarone and desethylamiodarone in therapeutic monitoring or emergency toxicology.

Effect of amiodarone on the phospholipid and lamellar body content of lymphoblasts in vitro and peripheral blood lymphocytes in vivo

Amiodarone is useful for the treatment of ventricular arrhythmias but has been associated with a significant degree of toxicity especially to lung and liver. The drug produces phospholipid accumulation in multilamella lysosomal inclusions in many tissues due to the ability of amiodarone and desethylamiodarone to inhibit phospholipase A. The adverse effects do not correlate with the plasma levels of amiodarone but relate more closely to the cumulative dose. No clear way of predicting amiodarone toxicity has yet emerged. In this report, normal human lymphoblasts in tissue culture were shown by electron microscopy to have dose-dependent increases in multilamellar inclusions when grown with amiodarone at concentrations which are routinely observed in patients receiving the drug. The content of phospholipid also increased but this parameter was not as sensitive as the number of multilamellar inclusions. Finally, lymphocytes from patients treated with amiodarone were examined by electron microscopy and shown to have increased numbers of multilamellar bodies.

Amiodarone and desethylamiodarone distribution in the atrium and adipose tissue of patients undergoing short- and long-term treatment with amiodarone

The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the heart. Amiodarone and desethylamiodarone, its active metabolite, were measured in the plasma, atrial tissue and pericardial fat of patients undergoing cardiac surgery. Two groups were studied: patients treated with amiodarone for less than 28 days (short-term group) and those treated for 28 days or more (long-term group). Plasma levels of amiodarone in the two groups were not different, whereas levels of desethylamiodarone were significantly higher in the long-term group. Average concentrations of amiodarone in the atrium were higher with longer treatment periods (30.2 +/- 5.6 versus 13.2 +/- 2.5 micrograms/g wet weight of tissue); the same was true for desethylamiodarone (40.3 +/- 7.7 versus 15.7 +/- 3.7 micrograms/g). Amiodarone concentrations in fat were also significantly higher in the long-term than in the short-term group. Atrium/plasma concentration ratios of desethylamiodarone were higher than those of amiodarone, whereas fat plasma concentration ratios of desethylamiodarone were lower. In conclusion, the equilibration of amiodarone and desethylamiodarone concentrations between myocardium and plasma appears to occur slowly in patients undergoing long-term treatment with amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)