Summary
The distribution and elimination of intravenous digoxin were investigated in seven neonates and infants with heart failure. Serum digoxin concentrations during a 24 h period were determined by radioimmunoassay, using125I as tracer. The serum values declined biexponentially after the injection and could be fitted to a two-compartment open model by non-linear least-squares regression. The calculated mean half-lives of the distribution (alpha) phase in neonates and infants were 37 and 28 min, respectively. The mean half-life of the elimination (beta) phase in neonates was 44 h, as compared to 19 h in infants. The mean volume of the central compartment and the mean volume of distribution at steady-state were calculated to be 1.3 and 9.9 l/kg, respectively; no significant differences between neonates and infants were found. The relation between these volumes indicates that digoxin is extensively distributed in tissues. The steady-state distribution volumes of digoxin in neonates and infants exceed those reported in adults. The larger volume of distribution might explain in part why infants with cardiac insufficiency require larger doses of digoxin than adults (on a mg/kg body weight basis) to obtain the same serum concentrations. Elimination of digoxin from the body was slower in neonates than in infants.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andersson, K.-E., Bertler, Å., Wettrell, G.: Post-mortem distribution and tissue concentrations of digoxin in infants and children. Acta paediat. scand.64, 497–504 (1975)
Bertler, Å., Redfors, A.: An improved method of estimating digoxin in human plasma. Clin. Pharmacol. Ther.11, 665–673 (1970)
Crawford, J.D., Terry, M.E., Rourke, G.M.: Simplification of drug dosage calculation by application of the surface area principle. Pediatrics5, 783–790 (1950)
Dengler, H.J., Bodem, G., Wirth, K.: Pharmacokinetic and metabolic studies with Lanatoside C, α- and β-acetyldigoxin and digoxin in man. Proc. 5th Int. Cong. Pharmacology. San Francisco, 1972, vol. 3, pp 112–126. Basel: Karger 1973
Dungan, W.T., Doherty, J.E., Harvey, C., Char, F., Dalrymple, G.W.: Tritiated digoxin XVIII: Studies in infants and children. Circulation46, 983–988 (1972)
Friis-Hansen, B.: Body composition during growth. Pediatrics47, 264–274 (1971)
Gibaldi, M., Nagashima, R., Levy, G.: Relationship between drug concentration in plasma or serum and amount of drug in the body. J. pharm. Sci.58, 193–197 (1969)
Gorodischer, R., Krasner, J., Yaffe, S.J.: Serum protein binding of digoxin in newborn infants. Research Comm. chem. Path. Pharmacol.9, 387–390 (1974)
Hernandez, A., Bruton, R.M., Pagtakhan, R.D., Goldring, D.J.: Pharmacodynamics of3H-digoxin in infants. Pediatrics44, 418–427 (1969)
Iisalo, E., Dahl, M.: Serum levels and renal excretion of digoxin during maintenance therapy in children. Acta paediat. scand.63, 699–704 (1974)
Jusko, W.J., Gibaldi, M.: Effects of change in elimination on various parameters of the two-compartment open model. J. pharm. Sci.61, 1270–1273 (1972)
Koup, J.R., Greenblatt, D.J., Jusko, W.J., Smith, T.W., Koch-Weser, J.: Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. J. Pharmacokin. Biopharm.3, 181–192 (1975a)
Koup, J.R., Jusko, W.J., Elwood, C.M., Kohli, R.K.: Digoxin pharmacokinetics. Role of renal failure in dosage regimen design. Clin. Pharmacol. Ther.18, 9–21 (1975b)
Lukas, D.S., De Martino, A.G.: Binding of digitoxin and some related cardenolides to human plasma proteins. J. clin. Invest.48, 1041–1053 (1969)
Morselli, P.L., Assael, B.M., Gomeni, R., Mandelli, M., Marini, A., Reali, E., Visconti, U., Sereni, F.: Digoxin pharmacokinetics during human development. Basic and therapeutic aspects of perinatal pharmacology (ed. Morselli, L., Garattini, S. and F. Sereni), p. 377–392, New York: Raven Press 1975
Nyberg, L., Andersson, K.-E., Bertler, Å.: Bioavailability of digoxin from tablets. II. Radioimmunoassay and disposition pharmacokinetics of digoxin after intravenous administration. Acta pharm. suecia11, 459–470 (1974)
Reuning, R.H., Sams, R.A., Notari, R.E.: 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)
Riegelman, S., Loo, I.C.K., Rowland, M.: Shortcomings in pharmacokinetic analyses by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci.57, 117–123 (1968)
Riggs, D.S.: The mathematical approach to physiological problems, p. 193–220, Baltimore, Maryland: Williams and Wilkins 1963
Taubert, K., Shapiro, W.: serum digoxin levels using an125I-labelled antigen: Validation of method and observations on cardiac patients. Amer. Heart J.89, 79–86 (1975)
Wagner, J.G., Northam, I.T., Alway, C.D., Carpenter, O.S.: Blood levels of drug at the equilibrium state after multiple dosing. Nature (Lond.)207, 1301–1302 (1965)
Wettrell, G., Andersson, K.-E., Bertler, Å., Lundström, N.R.: Concentrations of digoxin in plasma and urine in neonates, infants and children with heart disease. Acta paediat. scand.63, 705–710 (1974)
Wettrell, G., Andersson, K.-E.: Absorption of digoxin in infants. Europ. J. clin. Pharmacol.9, 49–55 (1975)
Yanagi, R., Kim, W.P., Krasula, R.W., Soyka, L.F., Hastreiter, A.R.: Urinary excretion of digoxin in infants and children. Circulation49–50, (Suppl. 3) abs No. 484, 1974
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wettrell, G. Distribution and elimination of digoxin in infants. Eur J Clin Pharmacol 11, 329–335 (1977). https://doi.org/10.1007/BF00566529
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00566529