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Verteilung von Digoxin, Digitoxin und ihren kardioaktiven Metaboliten im menschlichen Herz- und Nierengewebe

Distribution of digoxin, digitoxin and their cardioactive metabolites in the human heart and kidney—A post-mortem study

Eine post mortem-Untersuchung

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Summary

A method was developed for the specific determination of digoxin and digitoxin, as well as their semisynthetic derivatives and dependent cardioactive metabolites, in autopsy samples of heart and kidney.

A collective of six patients on long-term treatment with therapeutic doses of β-acetyldigoxin had a mean myocardial digoxin content of 46.1±25.0 ng/g (SD); kidney: 50.3±30.3 ng/g. Digoxigenin bisdigitoxoside represented the second most important metabolite in heart and kidney; digoxigenin monodigitoxoside and digoxigenin follow, respectively.

In a collective of seven patients on maintenance treatment with digitoxin, the mean tissue levels were higher but the metabolic pattern was similar (myocardial digitoxin content: 78.9±38.4 ng/g, renal content: 104.1±44.1 ng/g). The amount of digoxin formed by hydroxylation under long-term treatment with digitoxin in heart and kidney were approximately 10 ng/g.

A case of digoxin intoxication differed both in the tissue content and in the metabolic distribution.

Zusammenfassung

Es wurde ein Verfahren entwickelt zur monospezifischen Bestimmung von Digoxin, Digitoxin, ihren halbsynthetischen Derivaten und abhängigen kardioaktiven Metaboliten in postmortalen Gewebeproben von Herz und Niere.

Ein Kollektiv von sechs therapeutisch mit β-Acetyldigoxin behandelten Patienten zeigte einen mittleren myokardialen Digoxinspiegel von 46,1±25,0 ng/g (SD); Niere: 50,3±30,3 ng/g. Digoxigenin-bisdigitoxosid bildete den quantitativ zweitbedeutendsten Metaboliten in Herz und Niere. Digoxigenin-monodigitoxosid und Digoxigenin folgten in der Abstufung.

Ein therapeutisches Digitoxin-Kollektiv (n=7) wies durchgehend höhere Gewebespiegel auf, zeigte aber ein ähnliches Metabolitenmuster (Digitoxin-Gehalt des Herzens: 78,9±38,4 ng/g; Niere: 104,1±44,1 ng/g). Der Anteil des durch Hydroxylierung entstehenden Digoxins unter Digitoxin-Dauertherapie lag in Herz und Niere im Mittel bei 10 ng/g.

Eine Digoxin-Intoxikation unterschied sich sowohl im Gewebegehalt als auch in der relativen Verteilung der Metabolite.

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Literatur

  1. Aderjan R (1981) Tödliche Vergiftungen mit Herzglykosiden. Nachweis und rechtsmedizinisch toxikologische Befundbewertung. Habilitationsschrift Heidelberg

  2. Aderjan R (1983) Digitoxin-Konzentrationen in postmortal entnommenen Blut-und Gewebeproben des Menschen nach therapeutischer Dosierung. In: Gillmann H, Storstein L (Hrsg) Digitalistherapie heute. Verlag für angewandte Wissenschaften, München, S 49–57

    Google Scholar 

  3. Aderjan R, Mattern R (1980) Zur Wertigkeit postmortaler Digoxin-Konzentrationen im Blut. Z Rechtsmed 86:13–20

    Google Scholar 

  4. Benthe HF (1971) Renale Ausscheidungsprodukte von Alpha- und Beta-Acetyldigoxin. Therapiewoche 21:2186–2190

    Google Scholar 

  5. Benthe HF (1975) Organverteilung verschiedener Herzglykoside. In: Jahrmärkter H (Hrsg) Digitalistherapie. Springer Verlag, New York, S 19–37

    Google Scholar 

  6. Bergmann K, Abshagen U, Rietbrock N (1972) Quantitative analysis of digoxin, 4′″-acetyldigoxin and 4′″-methyldigoxin and their metabolites in bile and urine of rats. Arch Pharmacol 273:154–167

    Google Scholar 

  7. Biddle TL, Weintraub M, Lasagna L (1978) Relationship of serum and myocardial digoxin concentration to electrocardiographic estimation of digoxin intoxication. J Clin Pharmacol 18:10–15

    Google Scholar 

  8. Brisse B, Müller KM, Bender F, Harder K (1977) Digoxinspiegel in verschiedenen Abschnitten des menschlichen Myokards. Verh Dtsch Ges Inn Med 83:1673–1676

    Google Scholar 

  9. Caroll PR, Gelbart A, O'Rourke MF, Shortus J (1973) Digoxin concentrations in the serum and myocardium of digitalised patients. Aust NZJ Med 3:400–403

    Google Scholar 

  10. Coltart J, Howard M, Chamberlain D (1972) Myocardial and skeletal muscle concentrations of digoxin in patients on longterm therapy. Br Med J 2:318–319

    Google Scholar 

  11. Doherty JE, Perkins WH, Ackerman GL (1967) The distribution and concentration of tritiated digoxin in human tissues. Ann Intern Med 66:116–124

    Google Scholar 

  12. Doherty JE, Kane JJ (1973) Clinical pharmacology and therapeutic use of digitalis glycosides. Drugs 6:182–221

    Google Scholar 

  13. Gault MH, Longerich LL, Loo JCK, Ko PTH, Fine A, Vasdev SC, Dawe MA (1984) Digoxin biotransformation. Clin Pharmacol Ther 35:74–82

    Google Scholar 

  14. Graves PE, Perrier D, Marcus FI (1983) Quantitation of digitoxin and the bis- and monodigitoxosides of digitoxigenin in serum. J Chromatogr 278:397–405

    Google Scholar 

  15. Güllner HG, Stinson EB, Harrison DC, Kalman SM (1974) Correlation of serum concentrations with heart concentrations of digoxin in human subjects. Circulation 50:653–655

    Google Scholar 

  16. Haasis R, Larbig D, Stunkat R, Bader H, Seboldt H (1977) Radioimmunologische Bestimmung der Glykosidkonzentration im menschlichen Gewebe. Klin Wochenschr 55:23–30

    Google Scholar 

  17. Iisalo E, Nuutila M (1973) Myocardial digoxin concentrations in fatal intoxications. Lancet I:257

    Google Scholar 

  18. Karjalainen J, Ojala K, Reissel P (1974) Tissue concentrations of digoxin in autopsy material. Acta Pharmacol Toxicol 34:385–390

    Google Scholar 

  19. Loo JCK, McGilveray IJ, Jordan N (1977) Quantitation of digoxigenin in serum following oral administration of digoxin in humans. Res Comm Chem Path Pharmac 17:497–506

    Google Scholar 

  20. Loo JCK, McGilveray IJ, Jordan N (1981) The estimation of serum digoxin by combined HPLC separation and radioimmunological assay. J Liquid Chromatogr 4:879–886

    Google Scholar 

  21. Lukas DS (1971) Some aspects of the distribution and disposition of digitoxin in man. Ann NY Acad Sci 179:338–361

    Google Scholar 

  22. Margot PA, Finkle BS, Peat MA (1983) Analysis and problems of interpretation of digoxin in postmortem blood and tissues. Proc West Pharmacol Soc 26:393–396

    Google Scholar 

  23. Morais JA, Zlotecki RA, Sakmar E, Stetson PL, Wagner JG (1981) Specific and sensitive assays for digoxin in plasma, urine and heart tissue. Res Comm Chem Path Pharmacol 31:285–298

    Google Scholar 

  24. Nelson HA, Lucas SV, Gibson TP (1979) Isolation by high performance liquid chromatography and quantitation by radioimmunoassay of therapeutic concentrations of digoxin and metabolites. J Chromatogr (Biomed Appl) 163:169–177

    Google Scholar 

  25. Okita GT, Talso PJ, Curry JH, Smith FD, Geiling EMK (1955) Metabolic fate of radioactive digitoxin in human subjects. J Pharmacol Exp Ther 115:371–379

    Google Scholar 

  26. Peters U, Hengels KJ, Hausamen TV, Grosse-Brockhoff F (1975) Einfluß von Rifampicin auf den Metabolismus des Digitoxins. Verh Dtsch Ges Inn Med 81:1675–1676

    Google Scholar 

  27. Plum J (1984) Postmortaler Nachweis von Digitalisglykosiden beim Menschen. Dissertation Düsseldorf

  28. Plum J, Daldrup T (1985) Separation of digoxin, digitoxin, their semi-synthetic derivatives and cardioactive metabolites by high-performance liquid chromatography (in Vorbereitung)

  29. Rietbrock N, Vöhringer HF, Kuhlmann I (1977) Der Metabolismus herzwirksamer Glykoside. Herz Kreislauf 9:825–832

    Google Scholar 

  30. Rietbrock N, Woodcock BG (1981) Pharmacokinetics of digoxin and derivatives. In: Greef K (ed) Cardiac glycosides. Handbook of experimental pharmacology, vol 56/II. Springer Verlag, Berlin Heidelberg New York, pp 31–56

    Google Scholar 

  31. Ruiz-Torres A, Burmeister H (1972) Stoffwechsel und Kinetik von β-Acetyldigoxin. Klin Wochenschr 50:191–195

    Google Scholar 

  32. Schmoldt A (1984) Untersuchungen zum Metabolismus der Digitalisglykoside. Beitr Gerichtl Med 42:95–101

    Google Scholar 

  33. Storstein L (1977) Studies on digitalis. X. Digitoxin metabolites in human myocardium and relationship between myocardial and serum concentrations of digitoxin in patients on maintenance treatment. Clin Pharm Ther 21:395–408

    Google Scholar 

  34. Vorpahl TE, Coe JI (1978) Correlations of ante and postmortem digoxin levels. J Forens Sci 23:329–334

    Google Scholar 

  35. Weinmann J, Hasford J, Kuhlmann J, Bippus PH, Lichey J, Rietbrock N (1979) Digoxinkonzentrationen in Plasma und Gewebe. Med Klin 74:613–619

    Google Scholar 

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  1. Institut für Rechtsmedizin der Universität Düsseldorf, Moorenstr. 5, D-4000, Düsseldorf 1, Bundesrepublik Deutschland

    Jörg Plum & Thomas Daldrup

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  1. Jörg Plum
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Plum, J., Daldrup, T. Verteilung von Digoxin, Digitoxin und ihren kardioaktiven Metaboliten im menschlichen Herz- und Nierengewebe. Z Rechtsmed 94, 257–272 (1985). https://doi.org/10.1007/BF00205094

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  • DOI: https://doi.org/10.1007/BF00205094

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