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. 1993 Feb;35(2):136–142. doi: 10.1111/j.1365-2125.1993.tb05679.x

The bioavailability of digoxin from three oral formulations measured by a specific h.p.l.c. assay.

A F Cohen 1, R Kroon 1, H C Schoemaker 1, D D Breimer 1, A Van Vliet-Verbeek 1, H C Brandenburg 1
PMCID: PMC1381504  PMID: 8443031

Abstract

1. We have studied the absolute bioavailability of three oral formulations of digoxin, 1.0 mg, in 12 young healthy volunteers in a four way randomised cross-over study using an intravenous control. 2. Digoxin tablets (250 micrograms), liquid filled digoxin capsules (100 micrograms) and an experimental enteric-coated capsule (100 micrograms) were evaluated. In vitro dissolution at pH 1 demonstrated extensive hydrolytic breakdown of digoxin from the tablets and capsules but not from the enteric-coated capsules. 3. Serum 'digoxin' concentrations were measured by fluorescence polarization immunoassay (FPI). The systemic availability (+/- s.d.) of the capsules was 70.5 +/- 11.3%, and that of the tablets 71.5 +/- 8.6%. Drug was less available from the enteric-coated capsules (62.1 +/- 10.3%) measured with FPI. These results were reflected in the urinary drug recoveries measured by FPI. 4. By contrast, there were no differences in urinary recovery of unchanged digoxin between any of the oral treatments, when this was measured by h.p.l.c. The cross-reactivity of immunoassays for metabolites of digoxin may produce artefactual results and the optimal pharmaceutical formulation for digoxin remains to be determined.

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Selected References

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  1. Bustrack J. A., Katz J. D., Hull J. H., Foster J. R., Hammond J. E., Christenson R. H. Bioavailability of digoxin capsules and tablets: effect of coadministered fluid volume. J Pharm Sci. 1984 Oct;73(10):1397–1400. doi: 10.1002/jps.2600731018. [DOI] [PubMed] [Google Scholar]
  2. Böttcher H., Lüllmann H., Proppe D. Comparison of digoxin with some digitoxin metabolites on cat heart lung preparation. Eur J Pharmacol. 1973 Apr;22(1):109–111. doi: 10.1016/0014-2999(73)90192-1. [DOI] [PubMed] [Google Scholar]
  3. Cohen A. F., Kroon R., Schoemaker R., Hoogkamer H., van Vliet A. Influence of gastric acidity on the bioavailability of digoxin. Ann Intern Med. 1991 Oct 1;115(7):540–545. doi: 10.7326/0003-4819-115-7-540. [DOI] [PubMed] [Google Scholar]
  4. Embree L., McErlane K. M. Development of a high-performance liquid chromatographic-post-column fluorogenic assay for digoxin in serum. J Chromatogr. 1989 Nov 24;496(2):321–334. [PubMed] [Google Scholar]
  5. Forester W., Lewis R. P., Weissler A. M., Wilke T. A. The onset and magnitude of the contractile response to commonly used digitalis glycosides in normal subjects. Circulation. 1974 Mar;49(3):517–521. doi: 10.1161/01.cir.49.3.517. [DOI] [PubMed] [Google Scholar]
  6. Gault H., Kalra J., Ahmed M., Kepkay D., Barrowman J. Influence of gastric pH on digoxin biotransformation. I. Intragastric hydrolysis. Clin Pharmacol Ther. 1980 Jan;27(1):16–21. doi: 10.1038/clpt.1980.3. [DOI] [PubMed] [Google Scholar]
  7. Gault H., Kalra J., Ahmed M., Kepkay D., Longerich L., Barrowman J. Influence of gastric pH on digoxin biotransformation. II. Extractable urinary metabolites. Clin Pharmacol Ther. 1981 Feb;29(2):181–190. doi: 10.1038/clpt.1981.29. [DOI] [PubMed] [Google Scholar]
  8. Gault H., Kalra J., Longerich L., Dawe M. Digoxigenin biotransformation. Clin Pharmacol Ther. 1982 Jun;31(6):695–704. doi: 10.1038/clpt.1982.98. [DOI] [PubMed] [Google Scholar]
  9. Gibson T. P., Nelson H. A. The question of cumulation of digoxin metabolites in renal failure. Clin Pharmacol Ther. 1980 Feb;27(2):219–223. doi: 10.1038/clpt.1980.34. [DOI] [PubMed] [Google Scholar]
  10. Johnson B. F., Bye C., Jones G., Sabey G. A. A completely absorbed oral preparation of digoxin. Clin Pharmacol Ther. 1976 Jun;19(6):746–751. doi: 10.1002/cpt1976196746. [DOI] [PubMed] [Google Scholar]
  11. Johnson B. F., Lindenbaum J., Budnitz E., Marwaha R. Variability of steady-state digoxin kinetics during administration of tablets or capsules. Clin Pharmacol Ther. 1986 Mar;39(3):306–312. doi: 10.1038/clpt.1986.44. [DOI] [PubMed] [Google Scholar]
  12. Kuhlmann J., Abshagen U., Rietbrock N. Pharmacokinetics and metabolism of digoxigenin-mono-digitoxoside in man. Eur J Clin Pharmacol. 1974;7(2):87–94. doi: 10.1007/BF00561320. [DOI] [PubMed] [Google Scholar]
  13. Lindenbaum J., Mellow M. H., Blackstone M. O., Butler V. P., Jr Variation in biologic availability of digoxin from four preparations. N Engl J Med. 1971 Dec 9;285(24):1344–1347. doi: 10.1056/NEJM197112092852403. [DOI] [PubMed] [Google Scholar]
  14. Lindenbaum J., Rund D. G., Butler V. P., Jr, Tse-Eng D., Saha J. R. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med. 1981 Oct 1;305(14):789–794. doi: 10.1056/NEJM198110013051403. [DOI] [PubMed] [Google Scholar]
  15. Loo J. C., McGilveray I. J., Jordan N. Quantitation of digoxigenin in serum following oral administration of digoxin in humans. Res Commun Chem Pathol Pharmacol. 1977 Jul;17(3):497–506. [PubMed] [Google Scholar]
  16. Magnusson J. O., Bergdahl B., Bogentoft C., Jonsson U. E., Tekenbergs L. Excretion of digoxin and its metabolites in urine after a single oral dose in healthy subjects. Biopharm Drug Dispos. 1982 Jul-Sep;3(3):211–218. doi: 10.1002/bdd.2510030304. [DOI] [PubMed] [Google Scholar]
  17. Mallis G. I., Schmidt D. H., Lindenbaum J. Superior bioavailability of digoxin solution in capsules. Clin Pharmacol Ther. 1975 Dec;18(6):761–768. doi: 10.1002/cpt1975186761. [DOI] [PubMed] [Google Scholar]
  18. Mann H., Peters T. The cardioactivity of digitoxin metabolites. Eur J Pharmacol. 1971 Apr;14(2):204–205. doi: 10.1016/0014-2999(71)90213-5. [DOI] [PubMed] [Google Scholar]
  19. Marcus F. I., Ryan J. N., Stafford M. G. The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay. J Lab Clin Med. 1975 Apr;85(4):610–620. [PubMed] [Google Scholar]
  20. Shepard T. A., Hui J., Chandrasekaran A., Sams R. A., Reuning R. H., Robertson L. W., Caldwell J. H., Donnerberg R. L. Digoxin and metabolites in urine and feces: a fluorescence derivatization--high-performance liquid chromatographic technique. J Chromatogr. 1986 Jul 11;380(1):89–98. doi: 10.1016/s0378-4347(00)83627-0. [DOI] [PubMed] [Google Scholar]
  21. Sonobe T., Hasumi S., Yoshino T., Kobayashi Y., Kawata H., Nagai T. Digoxin degradation in acidic dissolution medium. J Pharm Sci. 1980 Apr;69(4):410–413. doi: 10.1002/jps.2600690412. [DOI] [PubMed] [Google Scholar]
  22. WEISSLER A. M., GAMEL W. G., GRODE H. E., COHEN S., SCHOENFELD C. D. THE EFFECT OF DIGITALIS ON VENTRICULAR EJECTION IN NORMAL HUMAN SUBJECTS. Circulation. 1964 May;29:721–729. doi: 10.1161/01.cir.29.5.721. [DOI] [PubMed] [Google Scholar]
  23. Warrington S. J., Turner P., Skrumsager B. K. Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine--a comparison with amitriptyline and placebo in healthy men. Br J Clin Pharmacol. 1989 Mar;27(3):343–351. doi: 10.1111/j.1365-2125.1989.tb05375.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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