Advertisement

European Journal of Clinical Pharmacology

, Volume 18, Issue 1, pp 69–74 | Cite as

Pharmacokinetics and dosage of digoxin in neonates and infants

  • L. Nyberg
  • G. Wettrell
Article

Summary

As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (>1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients.

The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.

Key words

digoxin neonates infants pharmacokinetics dosage schedules 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Levine OR, Blumenthal S (1962) Digoxin dosage in premature infants. Pediatrics 29: 18–25Google Scholar
  2. 2.
    Levy AM, Leaman DM, Hanson JS (1972) Effects of digoxin on systolic time intervals of neonates and infants. Circulation 46: 816–823Google Scholar
  3. 3.
    Nyberg L, Wettrell G (1978) Digoxin dosage schedules for neonates and infants based on pharmacokinetic considerations. Clin Pharmacokinet 3: 453–461Google Scholar
  4. 4.
    Pinsky WW, Jacobsen JR, Gillette PC, Adams J, Monroe L, McNamara DG (1979) Dosage of digoxin in premature infants. J Pediatr 96: 639–642Google Scholar
  5. 5.
    Halkin H, Radomsky M, Blieden L, Frand M, Millman P, Boichis H (1978) Steady state serum digoxin concentration in relation to digitalis toxicity in neonates and infants. Pediatrics 61: 184–188Google Scholar
  6. 6.
    Berman W Jr, Dubynsky O, Whitman V, Friedman Z, Maisels MJ, Musselman J (1978) Digoxin therapy in low-birth-weight infants with patent ductus arteriosus. J Pediatr 93: 652–655Google Scholar
  7. 7.
    Hayes CJ, Butler VP Jr, Gersony WM (1973) Serum digoxin studies in infants and children. Pediatrics 52: 561–568Google Scholar
  8. 8.
    Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB (1971) Digitalis intoxication. A prospective clinical study with serum level correlations. N Engl J Med 284: 989–997Google Scholar
  9. 9.
    Redfors A (1971) The effect of different digoxin doses on subjective symptoms and physical working capacity in patients with atrial fibrillation. Acta Med Scand 190: 307–320Google Scholar
  10. 10.
    Aronson JK, Grahame-Smith DG (1976) Digoxin therapy: Textbooks, theory, and practice. Br J Clin Pharmacol 3: 639–648Google Scholar
  11. 11.
    Sheiner LB (1974) The use of serum concentrations of digitalis for quantitative therapeutic decisions. Cardiovasc Clin 6: 141–151Google Scholar
  12. 12.
    Smith TW (1975) Digitalis toxicity: Epidemiology and clinical use of serum concentration measurements. Am J Med 58: 470–476Google Scholar
  13. 13.
    Iisalo E (1977) Clinical pharmacokinetics of digoxin. Clin Pharmacokinet 2: 1–16Google Scholar
  14. 14.
    Nyberg L, Andersson K-E, Bertler Å (1974) Bioavailability of digoxin from tablets. III. Availability of digoxin in man from preparations with different dissolution rate. Acta Pharm Suec 11: 471–492Google Scholar
  15. 15.
    Wettrell G, Andersson K-E (1975) Absorption of digoxin in infants. Eur J Clin Pharmacol 9: 49–55Google Scholar
  16. 16.
    Greenblatt DJ, Duhme DW, Koch-Weser J, Smith TW (1973) Evaluation of digoxin bioavailability in single-dose studies. N Engl J Med 289: 651–654Google Scholar
  17. 17.
    Steiness E, Rasmussen F, Svendsen O (1974) Plasma digoxin after parenteral administration. Local reaction after intramuscular administration. Clin Pharm Ther 16: 430–434Google Scholar
  18. 18.
    Morselli PL, Assael BM, Gomeni R, Mandelli M, Marini A, Reali E, Visconti V, Sereni F (1975) Digoxin pharmacokinetics during human development. In: Morselli PL, Garattini S, Sereni F (eds) Basic and therapeutic aspects of perinatal pharmacology. Raven Press, New York, pp 377–392Google Scholar
  19. 19.
    Wettrell G (1977) Distribution and elimination of digoxin in infants. Eur J Clin Pharmacol 11: 329–335Google Scholar
  20. 20.
    Svenningsen NW (1975) Single injection polyfructosan clearance in normal and asphyxiated neonates. Acta Paediatr Scand 64: 87–95Google Scholar
  21. 21.
    Leake RD, Trygstad CW (1977) Glomerular filtration rate during the period of adaptation to extrauterine life. Pediatr Res 11: 959–962Google Scholar
  22. 22.
    Digoxin labeling guidelines (adult and pediatric) (1976) Federal Register 41: 17759–17761Google Scholar
  23. 23.
    Lang D, v. Bernuth G (1977) Serum concentration and serum half-life of digoxin in premature and mature newborns. Pediatrics 59: 902–906Google Scholar
  24. 24.
    Lang D, Hofstetter R, v. Bernuth G (1978) Plasma digoxin concentration in different age groups. (In German, summary in English). Klin Wochenschr 56: 93–95Google Scholar
  25. 25.
    Lang D, Hofstetter R, v. Bernuth G (1978) Digoxin intoxication in newborns. Correlation with digoxin plasma concentration. (In German, summary in English). Monatsschr Kinderheilk 126: 148–152Google Scholar
  26. 26.
    Coltart DJ (1973) Alterations in the sensitivity of the human heart to digoxin. Int Res Commun System 73-3: 13Google Scholar
  27. 27.
    Hofstetter R, Lang D, v. Bernuth G (1979) Effect of digoxin on left ventricular contractility in newborns and infants estimated by echocardiography. Eur J Cardiol 9: 1–11Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • L. Nyberg
    • 1
  • G. Wettrell
    • 2
  1. 1.Research and Development DepartmentAB Draco (Subsidiary of AB Astra)LundSweden
  2. 2.Department of PaediatricsKärnsjukhusetSkövdeSweden

Personalised recommendations