Summary
In 23 patients treated with the iodine-containing antiarrhythmic drug amiodarone, the plasma concentrations of amiodarone, desethylamiodarone and iodine have been studied. Besides amiodarone and desethylamiodarone, a pool of iodine-containing substances, NANDAI (non-amiodarone-, non-desethylamiodarone-iodine), was present. At steady state the iodine content of NANDAI amounted to 64% and the iodine content of amiodarone plus desethylamiodarone to 36% of total serum iodine. At steady state 26% of the NANDAI fraction was made up of inorganic iodide, the average plasma concentration of which was at least 40 times above the upper limit of the normal range. The serum elimination half-life of NANDAI of 57–160 days exceeded that of amiodarone (35–68 days) and of desethylamiodarone (31–110 days).
At steady state the serum concentration of desethylamiodarone appears to be related to the concentration of amiodarone by a Michaelis-Menten type function, yielding a Km of amiodarone of 2.45 µmol/l and a maximal desethylamiodarone concentration of 3.61 µmol/l.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Broekhuysen J, Laruel R, Sion R (1969) Recherches dans la série des benzofurannes XXXVII. Etude comparée du transit et du métabolisme de l'amiodarone chez diverses espèces animales et chez l'homme. Arch Int Pharmacodyn Ther 177: 340–359
Kannan R, Nademanee K, Hendrickson JA, Rostami HJ, Singh BN (1982) Amiodarone kinetics after oral doses. Clin Pharmacol Ther 31: 438–451
Holt DW, Tucker GT, Jackson PR, Storey GCA (1983) Amiodarone pharmacokinetics. Am Heart J 106: 840–847
Stäubli M, Bircher J, Galeazzi RL, Remund H, Studer H (1983) Serum concentrations of amiodarone during long-term therapy. Relation to dose, efficacy and toxicity. Eur J Clin Pharmacol 24: 485–494
Storey GCA, Holt DW, Holt P, Curry PVL (1982) High-performance liquid chromatographic measurement of amiodarone and its desethyl metabolite: Methodology and preliminary observations. Ther Drug Monit 4: 385–388
Harris L, Hind CRK, McKenna WJ, Savage C, Krikler SJ, Storey GCA, Holt DW (1983) Renal elimination of amiodarone and its desethyl metabolite. Postgrad Med J 59: 440–442
Rotmensch HH, Belhassen B, Swanson BN, Shoshani D, Spielman SR, Greenspon AJ, Greenspan AM, Vlasses PH, Horowitz LN (1984) Steady state serum amiodarone concentrations: relationship with antiarrhythmic efficacy and toxicity. Ann Intern Med 101: 462–469
Lauber K (1975) Iodine determination in biological material. Kinetic measure of the catalytic activity of iodine. Anal Chem 47: 769–771
Sterling K (1974) The nature of iodine in plasma. In: Handbook of physiology, sect. 7: Endocrinology Vol III: Thyroid. Greer MA, Solomon DH (eds) Waverly Press, Baltimore, pp 179–186
Sachs L (1974) Angewandte Statistik, 4th edition. Springer, Berlin Heidelberg New York
Andreasen F, Agerbaek H, Bjerregaard P, Gotzsche H (1981) Pharmacokinetics of amiodarone after intravenous and oral administration. Eur J Clin Pharmacol 19: 293–299
Nademanee K, Kannan R, Hendrickson JA, Burnann M, Kay I, Singh B (1982) Amiodarone-digoxin interaction during treatment of resistant cardiac arrhythmias. Am J Cardiol 49: 1026
Harris L, McKenna WJ, Rowland E, Holt DW, Storey GCA, Krikler DM (1983) Side-effects of long-term amiodarone therapy. Circulation 67: 45–51
Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JO, Elizari MV (1976) Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 38: 934–944
Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, Pacchiarotti A, Aronin N, Macchia E, Haffajee C, Odoguardi L, Love J, Bigalli A, Baschieri L, Pinchera A, Braverman L (1984) Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med 101: 28–34
Studer H, Ramelli F (1982) Simple goiter and its variants: Euthyroid and hyperthyroid multinodular goiters. Endocr Rev 3: 40–61
Stäubli M, Bischof P, Wimpfheimer C, Studer H (1981) Amiodaron (Cordarone) und Schilddrüse. Schweiz Med Wochenschr 111: 1590–1596
Savoie JC, Massin JP, Thomopoulos P, Leger F (1975) Iodine-induced thyrotoxicosis in aparently normal thyroid glands. J Clin Endocrinol 41: 685–691
Leger AF, Massin JP, Laurent MF, Vincens M, Auriol M, Helal OB, Chomette G, Savoie JC (1984) Iodine-induced thyrotoxicosis: Analysis of eighty-five consecutive cases. Eur J Clin Invest 14: 449–455
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stäubli, M., Troendle, A., Schmid, B. et al. Pharmacokinetics of amiodarone, desethylamiodarone and other iodine-containing amiodarone metabolites. Eur J Clin Pharmacol 29, 417–423 (1985). https://doi.org/10.1007/BF00613455
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00613455