Summary
The absorption of digoxin from a capsule preparation containing a large number of small, enteric-coated granules of the glycoside (Preparation CR) was compared in 10 volunteers with that from a rapidly dissolving tablet (Preparation L). Plasma and urine digoxin concentrations were measured by radioimmunoassay. In the fasting state, after a loading dose of digoxin (0.76 mg), peak plasma concentrations were significantly (p<0.001) lower after CR (2.0±0.5 nmol/l, mean±SD) than L (4.7±1.1 nmol/l). Peak concentrations after CR were significantly (p<0.001) delayed compared to L (3.3±0.6 h vs 1.1±0.4 h). Also, postprandial peak plasma concentrations at steady state, were significantly (p<0.01) lower after CR (1.0±0.3 nmol/l) than L (2.7±0.5 nmol/l), and the peak concentrations occurred later (3.9±1.7 h vs 1.4±0.9 h). The area under the plasma concentration-time curves was smaller (p<0.01) for CR (17.7±5.9 nmol·l−1·h) than for L (22.4±4.1 nmol·l−1·h), and so was the amount of drug excreted in urine (174±25 µg vs 190±31 µg; p<0.005). Thus, the absorption rate of digoxin from the enteric-coated formulation was markedly reduced but at the cost of a variable reduction in the amount absorbed.
Similar content being viewed by others
References
Andersson K-E, Nyberg L, Dencker H, Göthlin J (1975) Absorption of digoxin in man after oral and intrasigmoid administration. Eur J Clin Pharmacol 9: 39–47
Aronson JK (1980) Clinical pharmacokinetics of digoxin 1980. Clin Pharmacokinet 5: 137–149
Bertler Å, Medin S, Nyberg L, Redfors A (1972) Bioavailability of digoxin. Lancet 2: 708
Bergdahl B, Bogentoft C, Jonsson UE, Magnusson JO (1980) Absorption of digoxin from a new microencapsulated formulation. Eur J Clin Pharmacol 17: 443–447
Bogentoft C, Carlsson I, Ekenved E, Magnusson A (1978) Influence of food on the absorption of acetylsalicylic acid from enteric coated dosage forms. Eur J Clin Pharmacol 14: 351–355
Gault MH, Charles JD, Sugden DL, Kepkay DC (1977) Hydrolysis of digoxin by acid. J Pharm Pharmacol 29: 27–32
Gault H, Kalra J, Ahmed M, Kepkay D, Barrowman J (1980) Influence of gastric pH on digoxin biotransformation. I. Intragastric hydrolysis. Clin Pharmacol Ther 27: 16–21
Gerson CD, Lowe EH, Lindenbaum J (1980) Bioavailability of digoxin tablets in patients with gastrointestinal dysfunction. Am J Med 69: 43–49
Greenblatt DJ, Duhme DW, Koch-Weser J, Smith TW (1974) Bioavailability of digoxin tablets and elexir in the fasting and postprandial states. Clin Pharmacol Ther 16: 444–448
Johnson BF, O'Grady J, Sabey GA, Bye C (1978) Effect of a standard breakfast on digoxin absorption in normal subjects. Clin Pharmacol Ther 23: 315–319
Kuhlmann J, Abshagen U, Riebrock N (1973) Cleavage of glycosidic bonds of digoxin and derivates as function of pH and time. Naunyn-Schmiedeberg's Arch Pharmacol 276: 149–156
Lindenbaum J, Rund DG, Butler VP, Tse-Eng D, Saha JR (1981) Inactivation of digoxin by the gut flora: Reversal by antibiotic therapy. N Engl J Med 305: 789–794
Magnusson JO, Bergdahl B, Bogentoft C, Jonsson UE, Tekenbergs L (1982a) Excretion of digoxin and its metabolites in urine after a single oral dose in healthy subjects. Biopharm Drug Disp 3: 211–218
Magnusson JO, Bergdahl B, Bogentoft C, Jonsson UE (1982b) Metabolism of digoxin and absorption site. Br J Clin Pharmacol 14: 284–285
Manninen V, Reissell P, Pankkala E (1976) Transient cardiac arrhythmias after single daily maintenance doses of digoxin. Clin Pharmacol Ther 20: 266–268
Nyberg L, Bratt L, Forsgren A, Hugosson S (1974a) Bioavailability of digoxin from tablets. I. In vitro characterization of digoxin tablets. Acta Pharm Suec 11: 447–458
Nyberg L, Andersson K-E, Berler Å (1974b) Bioavailability of digoxin from tablets. III. Availability of digoxin in man from preparations with different dissolution rate. Acta Pharm Suec 11: 471–492
Osneas J-B (1978) Kardiale bivirkningar de forste timene etter digoxininntak. Tidsskr Nor Laegeforen 2: 92
Sanchez N, Sheiner LB, Halkin H, Melmon KL (1973) Pharmacokinetics of digoxin: Interpreting bioavailability. Br Med J 4: 132–134
Smith TW (1975) Digitalis toxicity: Epidemiology and clinical use of serum concentration measurements. Am J Med 58: 470–476
Sterson LA, Shaffer RD (1978) Kinetics of digoxin stability in aqueous solution. J Pharm Sci 67: 327–330
White RJ, Chamerlain DA, Howard M, Smith TW (1971) Plasma concentrations of digoxin after oral administration in the fasting and postprandial state. Br Med J 1: 380–381
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergdahl, B., Bogentoft, C., Jonsson, U.E. et al. Fasting and postprandial absorption of digoxin from a microencapsulated formulation. Eur J Clin Pharmacol 25, 207–210 (1983). https://doi.org/10.1007/BF00543792
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00543792