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Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses

Journal of Pharmacokinetics and Biopharmaceutics volume 3, pages 181–192 (1975)Cite this article

Abstract

Normal subjects were given 0.75 mg of intravenous digoxin as a bolus and a 1-hr infusion, Radio-immunoassayed serum concentrations obtained over 48 hr and urinary excretion rates over 6 days were simultaneously fitted to a two- compartment open model by computer nonlinear least-squares regression. Serum concentration data alone were also fitted by this program. There was good agreement in calculated parameters between the two routes of administration in five of eight subjects, but the infusion mode of administration produced less variability in the apparent pharmacokinetic constants. The β half-life values obtained from serum concentration data alone (24.2 hr) underestimated the half-lives obtained by the simultaneous fit (44.1 hr). The steady-state volume of distribution of digoxin averaged 590±164 liters (±1 sd).The renal clearance of digoxin (140±41 ml/min/1.73 m 2)was significantly higher than creatinine clearance (101±13 ml/min/ 1.73 m 2),indicating tubular secretion of the drug. Digoxin body clearances were 188±44 ml/min/ 1.73 m 2,indicating elimination of 25% of the dose by nonrenal mechanisms. Urinary excretion data are essential for proper pharmacokinetic analysis of digoxin disposition and reveal a slower rate of elimination than that suggested by earlier studies which determined only serum concentrations.

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References

  1. J. E. Doherty, W. J. Flanigan, and G. V. Dalrymple. Tritiated digoxin. XVII. Excretion and turnover times in normal donors before and after nephrectomy and in the paired recipients of the kidney after transplantation.Am. J. Cardiol. 29: 470–474 (1972).

    CAS  PubMed  Article  Google Scholar 

  2. H. J. Gilfrich, G. Bodem, and C. A. Chidsey. Untersuchungen zur Pharmakokinetik von Digoxin.Arzneim. Forsch. 23: 1659–1660 (1974).

    Google Scholar 

  3. R. H. Reuning, R. A. Sams, and R. E. Notari. Role of pharmacokinetics in drug dosage adjustment. I. Pharmacologic effect kinetics and apparent volume of distribution of digoxin.J. Clin. Pharmacol. 13: 127–141 (1973).

    CAS  Google Scholar 

  4. P. M. Bloom, W. B. Nelp, and S. H. Tuell. Relationship of the excretion of tritiated digoxin to renal function.Am. J. Med. Sci. 251: 133–144 (1966).

    CAS  PubMed  Article  Google Scholar 

  5. F. I. Marcus, A. Peterson, A. Salel, J. Scully, and G. G. Kapadia. The metabolism of tritiated digoxin in renal insufficiency in dogs and man.J. Pharmacol. Exp. Ther. 152: 372–382 (1966).

    CAS  PubMed  Google Scholar 

  6. W. Shapiro, K. Harahara, and K. Taubert. Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man.Circulation 42: 1065–1072 (1970).

    CAS  PubMed  Article  Google Scholar 

  7. D. J. Greenblatt, D. W. Duhme, J. Koch-Weser, and T. W. Smith. Intravenous digoxin as a bioavailability Standard; slow infusion and rapid injection.Clin. Pharmacol. Ther. 15: 510–513 (1974).

    CAS  PubMed  Google Scholar 

  8. C. M. Metzler. NONLIN: A Computer Program for Parameter Estimation in Nonlinear Situations, Upjohn Co., Kalamazoo, Mich., Technical Report No. 7292/69/7292/005, Nov. 25, 1969.

    Google Scholar 

  9. J. C. K. Loo and S. Riegelman. Assessment of pharmacokinetic constants from postinfusion blood curves obtained after IV infusion.J. Pharm. Sci. 59: 53–55 (1970).

    CAS  PubMed  Article  Google Scholar 

  10. W. J. Jusko and M. Gibaldi. Effects of change in elimination on various parameters of the two-compartment open model.J. Pharm. Sci. 61: 1270–1273 (1972).

    CAS  PubMed  Article  Google Scholar 

  11. C. I. Bliss.Statistics in Biology, Vol. 1, McGraw-Hill, New York, 1967, p. 211.

    Google Scholar 

  12. J. G. Wagner. Appraisal of digoxin bioavailability and pharmacokinetics in relation to cardiac therapy.Am. Heart. J. 88: 133–138 (1974).

    CAS  PubMed  Article  Google Scholar 

  13. R. G. Stoll, M. S. Christensen, E. Sakmar, and J. G. Wagner. The specificity of the digoxin radioimmunoassay procedure.Res. Commun. Chem. Pathol. Pharmacol. 4: 503–510 (1972).

    CAS  PubMed  Google Scholar 

  14. J. R. Koup, W. J. Jusko, C. M. Elwood, and R. K. Kohli. Digoxin pharmacokinetics: Role of renal failure in dosage regimen design.Clin. Pharmacol. Ther. 17 (1975), in press.

  15. P. R. Klink, R. I. Poust, J. L. Colaizzi, and R. H. McDonald. Bioavailability and dissolution properties of two commercial digoxin tablets.J. Pharm. Sci. 63: 1231–1234 (1974).

    CAS  PubMed  Article  Google Scholar 

  16. W. G. Kramer, R. P. Lewis, T. C. Cobb, W. F. Forester, J. A. Visconti, L. A. Wanke, H. G. Boxenbaum, and R. H. Reuning. Pharmacokinetics of digoxin: Comparison of a two- and three-compartment model in man.J. Pharmacokin. Biopharm. 2: 299–312 (1974).

    CAS  Article  Google Scholar 

  17. E. E. Ohnhaus, P. Spring, and L. Dettli. Eliminationskinetik und Dosierung von Digoxin bei Patienten mit Niereninsuffizienz.Deutsch. Med. Wschr. 99: 1797–1803 (1974).

    CAS  PubMed  Article  Google Scholar 

  18. L. B. Sheiner, B. Rosenberg, and K. L. Melmon. Modelling of individual pharmacokinetics for computer-aided drug dosage.Comp. Biomed. Res. 5: 441–459 (1972).

    Article  Google Scholar 

  19. E. Steiness. Renal tubular secretion of digoxin.Circulation 50: 103–107 (1974).

    CAS  PubMed  Article  Google Scholar 

  20. R. W. Jelliffe. An improved method of digoxin therapy.Ann. Int. Med. 69: 703–717 (1968).

    CAS  PubMed  Article  Google Scholar 

  21. G. A. Ewy, B. M. Groves, M. F. Ball, L. Nimmo, B. Jackson, and F. Marcus. Digoxin metabolism in obesity.Circulation 44: 810–814 (1971).

    CAS  PubMed  Article  Google Scholar 

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Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, State University of New York, 14214, Buffalo, New York

    Jeffrey R. Koup &  William J. Jusko

  2. Clinical Pharmacology and Cardiac Units, Department of Medicine, Massachusetts General Hospital, USA

    David J. Greenblatt, Thomas W. Smith & Jan Koch-Weser

  3. Department of Medicine, Harvard Medical School, 02114, Boston, Massachusetts

    David J. Greenblatt, Thomas W. Smith & Jan Koch-Weser

Authors
  1. Jeffrey R. Koup
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  2. David J. Greenblatt
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  3. William J. Jusko
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  4. Thomas W. Smith
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  5. Jan Koch-Weser
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Additional information

Supported in part by Grant 20852 from the National Institutes of General Medical Sciences, National Institutes of Health.

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Koup, J.R., Greenblatt, D.J., Jusko, W.J. et al. Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. Journal of Pharmacokinetics and Biopharmaceutics 3, 181–192 (1975). https://doi.org/10.1007/BF01067907

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  • DOI: https://doi.org/10.1007/BF01067907

Key words

  • digoxin
  • two-compartment model
  • pharmacokinetics
  • urinary excretion
  • radioimmunoassay