Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Amiodarontherapie — Verhalten von Serum- und Fettgewebskonzentrationen

Serum and fatty tissue concentrations of amiodarone

  • 15 Accesses

  • 4 Citations

Summary

Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200–600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r=0.56,p<0.001) as well as in subcutaneous fatty tissue (r=0.67,p<0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p<0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metablite (p<0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.

This is a preview of subscription content, log in to check access.

Abbreviations

A:

Amiodaron

DEA:

Desethylamiodaron

rT3 :

reverse T3

Literatur

  1. 1.

    Anastasiou-Nana M, Levis GM, Moulopulos S (1982) Pharmacokinetics of amiodarone after intravenous and oral administration. Int J Clin Pharmacol Ther Toxicol 20:524–529

  2. 2.

    Anderson GJ (1982) Antiarrhythmic actions of amiodarone. Clin Pharmacol Ther 25:178–180

  3. 3.

    Andreasen F, Agerbaek H, Bjerregaard P, Gotzsche H (1981) Pharmacokinetics of amiodarone after intravenous and oral administration. Europ J Clin Pharmacol 19:293–299

  4. 4.

    Andresen D, Tietze U, von Leitner ER, Lehmann HU, Thormann I, Schröder R (1980) Spontanvariabilität tachykarder Rhythmusstörungen. Z Kardiol 69:214

  5. 5.

    Broekhuysen J (1983) Pharmacology of amiodarone — History and prospects. In: Krikler DM, McKenna WJ, Chamberlain DA (eds) Amiodarone and Arrhythmias. Pergamon Press, Oxford pp 5–9

  6. 6.

    Broekhuysen J, Laurel R, Sion R (1969) Recherches dans la série des benzofuranes XXXVII. Etude comparée du transit et du métabolisme de l'amiodarone chez diverses espèces animales et chez l'homme. Arch Int Pharmacodyn Ther 188:340–359

  7. 7.

    Charlier R (1970) Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors. Brit J Pharmacol 39:668–674

  8. 8.

    Criée CP, Wilhelms E, Kneba M, Kreuzer H (1984) Multiple Rundherdbildungen in der Lunge während Amiodaron-Therapie. Dtsch med Wochenschr 109:499–500

  9. 9.

    Debbas N, du Caillar C, Bexton R, Demaille J, Camm AJ, Pueck P (1984) The QT-Interval: a predictor of the plasma and myocardial concentration of amiodarone. Br Heart J 51:316–320

  10. 10.

    Flanagan RJ, Storey GCA, Holt DW (1980) Rapid high performance liquid chromatographic method for the measurement of amiodarone in blood plasma or serum at the concentrations attained during therapy. J Chromatogr 187:391–398

  11. 11.

    Flanagan RJ, Storey GCA, Holt DW, Farmer PB (1982) Identification and measurement of desethylamiodarone in blood plasma specimens for amiodarone treated patients. J Pharm Pharmacol 34:638–643

  12. 12.

    Fogoros RN, Anderson KP, Winkle RA, Swerdlow CD, Mason JW (1983) Amiodarone: clinical efficacy and toxicity in 96 patients with recurrent, drug-refractory arrhythmias. Circulation 68:88–94

  13. 13.

    Graboys TB, Podrid PJ, Lown B (1983) Efficacy of amiodarone for refractory supraventricular tachyarrhythmias. Am Heart J 106:870–874

  14. 14.

    Haffajee CJ Klinische Pharmakokinetik oraler Amiodaron-Gaben. In: Breithardt G, Loogen F (Hrsg) Neue Aspekte in der medikamentösen Behandlung von Tachyarrhythmien — Die Bedeutung von Amiodaron. Urban & Schwarzenberg, München Wien Baltimore, S 63–71

  15. 15.

    Haffajee CJ, Love JC, Canada AT, Lesko LJ, Asdourian G, Alpert JS (1983) Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation 67:1347–1355

  16. 16.

    Harris L, McKenna WJ, Rowland E, Holt DW, Storey GCA, Krikler DM (1983) Side effects of long-term amiodarone therapy. Circulation 67:45–51

  17. 17.

    Heger JJ, Prystowsky EN, Zipes DP (1983) Clinical efficacy of amiodarone in treatment of recurrent ventricular tachycardia and ventricular fibrillation. Am Heart J 106:887–892

  18. 18.

    Heger JJ, Solow EB, Prystowsky EN, Zipes DP (1984) Plasma and red blood cell concentration of amiodarone during chronic therapy. Am J Cardiol 53:912–917

  19. 19.

    Hermann J (1983) Jodinduzierte Hyperthyreose. In: Breithardt G, Loogen F (Hrsg) Neue Aspekte in der medikamentösen Behandlung von Tachyarrhythmien — Die Bedeutung von Amiodaron. Urban & Schwarzenberg, München Wien Baltimore, S 258–262

  20. 20.

    Kannan R, Nademanee K, Hendrickson JA, Rostami HJ, Singh BN (1982) Amiodarone kinetics after oral doses. Clin Pharmacol Ther 31:438–444

  21. 21.

    Latini R, Tognoni G, Kates RE (1984) Clinical pharmacokinetics of amiodarone. Clin Pharmacokin 9:136–156

  22. 22.

    Maggioni AP, Maggi A, Volpi A, D'Aranno V, Tognoni G, Giani P (1983) Amiodarone distribution in human tissues after sudden death during Holter monitoring. Am J Cardiol 52:217–218

  23. 23.

    Morganroth J, Michelson EL, Horowitz N, Josephson ME, Pearlman AS, Dunkman WB (1978) Limitations of routine long-term electrocardiographic monitoring to assess ventricular ectopic frequency. Circulation 58:408–414

  24. 24.

    Nitsch J, Lüderitz B (1984) Kontrolle der antiarrhythmischen Therapie mit Amiodaron. Bedeutung der Serumspiegelbestimmung. Dtsch med Wochenschr 109:492–495

  25. 25.

    Nokin P, Clinet M, Schoenfeld P (1983) Cardiacβ-adrenoceptor modulation by amiodarone. Biochem Pharmac 32:2473–2477

  26. 26.

    Patterson E, Eller BT, Abrams GD, Vasiliades J, Lucchesi BR (1983) Ventricular fibrillation in a conscious canine preparation of sudden coronary death — prevention by short- and long-term amiodarone administration. Circulation 68:857–864

  27. 27.

    Plomp TA, van Rossum JM, Robles de Medina EO, van Lier T, Maes RAA (1984) Pharmacokinetics and body distribution of amiodarone. Arzneim-Forsch / Drug res 34:513–520

  28. 28.

    Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JD, Elizari MV (1976) Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 38:934–944

  29. 29.

    Singh BN, Jewitt DE, Downey JM, Kirk E, Sonnenblick EH (1976) Effects of amiodarone and L 8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary hemodynamics and on cardiac intracellular potentials. Clin Exp Pharmacol Physiol 3:427–442

  30. 30.

    Sobol SM, Rakita L (1982) Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: a possible complication of a new antiarrhythmic. Circulation 65:819–824

  31. 31.

    Stäubli M, Bircher J, Galezzi 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

  32. 32.

    Storey GCA, Holt DW (1982) High-performance liquid chromatographic measurement of amiodarone and desethylamiodarone in plasma or serum at the concentrations attained fellowing a single 400 mg dose. J Chromatogr 245:377–380

  33. 33.

    Storey GCA, Adams PC, Campbell RWF, Holt DW (1983) High performance liquid chromatographic measurement of amiodaron and desethylamiodarone in small samples after enzymatic digestion. J Clin Pathol 36:785–789

  34. 34.

    Waxman HL, Groh WC, Marchlinski FE, Baxton AE, Sadowski LM, Horowitz LN, Josephson ME, Kastor JA (1982) Amiodarone for control of sustained ventricular tachyarrhythmias: clinical and electrophysiologic effects in 51 patients. Am J Cardiol 50:1066–1074

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gonska, B.-., Bethge, K.-., Wagner, H. et al. Amiodarontherapie — Verhalten von Serum- und Fettgewebskonzentrationen. Klin Wochenschr 64, 219–226 (1986). https://doi.org/10.1007/BF01711651

Download citation

Key words

  • Amiodarone
  • Reverse T3
  • Antiarrhythmic efficacy