Summary
The intestinal absorption and urinary elimination rate of total cardioactive material was compared following digoxin and beta-methyldigoxin (BMD) administration to twelve healthy volunteers. Significantly more injected digoxin was recovered in urine. Urinary clearance was more rapid for digoxin, mean half-lives of elimination being 35 hours for digoxin and 40 hours for BMD. Calculated percentage intestinal absorption was lowest for digoxin tablets with a dissolution rate of 77% in one hour, intermediate for BMD tablets, and maximal for an experimental soft gelatin formulation of digoxin in solution. Respective mean values were 75%, 87% and 97%. Similar steady state plasma concentrations followed twice daily ingestion of the 0.25 mg digoxin tablets and 0.20 mg BMD tablets. Mean peak plasma concentration and percentage urinary recovery of ingested dose were higher during continued BMD administration. Between-subject variation in absorption was higher for the digoxin tablets. The comparative intestinal absorption of BMD and digoxin depends upon the formulation. Digoxin is virtually completely absorbed from a solution encapsulated in soft gelatin. Relatively more BMD is eliminated by nonrenal routes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wirth, K., Bodem, G., Dengler, H.J.: Kinetik und Stoffwechsel von Digoxin und verwandten Herzglykosiden beim Menschen. Naunyn-Schmiedeberg's Arch. Pharmacol.269, 427–428 (1971)
Beermann, B.: The gastrointestinal uptake of methyldigoxin-12α-3H in man. Europ. J. clin. Pharmacol.5, 28–33 (1972)
Mallis, G., Schmidt, D., Lindenbaum, J.: Superior bioavailability of digoxin solution in capsules. Clin. Pharmacol. Ther.18, 761–768 (1975)
Larbig, D., Kochsiek, K.: Zur radioimmunchemischen Bestimmung von Digoxin und Digoxinderivaten. Dtsch. med. Wschr.97, 1310–1312 (1972)
Greenwood, Helena, Snedden, W., Hayward, R.P., Landon, J.: The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy. Clin. chim. Acta.62, 213–224 (1975)
Johnson, B.F., Bye, C.: Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration. Brit. Heart J.37, 203–208 (1975)
Marcus, F.I., Peterson, A., Salel, A., Scully, J., Kapadia G.G.: The metabolism of tritiated digoxin in renal insufficiency in dogs and man. J. Pharmacol. exp. Ther.152, 372–382 (1965)
Doherty, J.E., Perkins, W.H.: Studies with tritiated digoxin in human subjects after intravenous administration. Amer. Heart J.63, 528–536 (1962)
Kramer, P., Scheler, F.: Renale Eliminationskinetik verschiedener Herzglykoside. Dtsch. med. Wschr.97, 1485–1490 (1972)
Rietbrock, N., Rennekamp, Ch., Rennekamp, H., v. Bergmann, K., Abshagen, U.: Demethylation and cleavage of glycosidic bonds of 4‴-methyldigoxin in man. Naunyn-Schmiedeberg's Arch. Pharmacol.272, 450–452 (1972)
Rennekamp, H., Rennekamp, Ch., Abshagen, U., v. Bergmann, K., Rietbrock, N.: Pharmacokinetic behaviour of 4‴-methyldigoxin in man. Naunyn-Schmiedeberg's Arch. Pharmacol.273, 172–174 (1972)
Marcus, F.I., Kapadia, G.J., Kapadia, G.G.: The metabolism of digoxin in normal subjects. J. Pharmacol. exp. Ther.145, 203–209 (1964)
Zilly, W., Richter, E., Rietbrock, N.: Pharmacokinetics and metabolism of digoxin- and beta-methyl-digoxin-12α-3H in patients with acute hepatitis. Clin. Pharmacol. Ther.17, 302–309 (1975)
Kramer, P., Hornekamp, J., Willms, B., Scheler, F.: Accumulation of various cardiac glycosides during anuria. Dtsch. med. Wschr.95, 444–454 (1970)
Larbig, D., Scheler, F., Schmidt, H.J., Betzien, G., Kaufmann, B.: Untersuchungen zur enteralen Resorption von Beta-methyldigoxin. Klin. Wschr.49, 604–607 (1971)
Belz, G.G., Kleeberg, U.R.: Plasma half life of beta-methyl digoxin following repetitive application in man. Klin. Wschr.53, 491–492 (1975)
Haasis, R., Larbig, D., Klenk, K.O.: Glykosidkonzentration im Serum und Urin bei Herzgesunden nach Gabe von Beta-Methyl-Digoxin. Klin. Wschr.53, 529–533 (1975)
Härtel, G., Manninen, V., Melin, J., Apajalahti, A.: Serum-digoxin concentration with a new digoxin derivative, beta-methyl digoxin. Ann. Clin. Res.5, 87–90 (1973)
Wildmeister, W., Strobach, H., Greeff, K., Horster, F.A.: Zur Pharmakokinetik von Digoxin, Acetyldigoxin und Methyldigoxin bei Gesunden und Kranken. Verh. dtsch. Ges. inn. Med.79, 1037–1039 (1973)
Lindenbaum, J.: Bioavailability of different lots of digoxin tablets from the same manufacturer. Clin. Pharmacol. Ther.17, 296–301 (1975)
Storz, H.: Die quantitative Wirksamkeit des Herzglykosids Beta-Methyl-Digoxin. Med. Welt (Berl.)21, 2066–2070 (1970)
Johnson, B.F., Lader, S.: Bioavailability of digoxin from rapidly dissolving preparations. Brit. J. Clin. Pharmacol.1, 329–333 (1974)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Johnson, B.F., Bye, C.E., Jones, G.E. et al. The pharmacokinetics of beta-methyl digoxin compared with digoxin tablets and capsules. Eur J Clin Pharmacol 10, 231–236 (1976). https://doi.org/10.1007/BF00558334
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00558334