Skip to main content
SpringerLink
Log in

Age-Related Differences in Digoxin Toxicity and its Treatment

  • Review Article
  • Drug Safety Concepts
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Digoxin toxicity remains a common medical problem for both adults and children. In addition to a vastly improved understanding of the mechanisms for digoxin action on the heart, there are now data which clearly demonstrate that there are potentially important developmental differences in both the pharmacodynamics and pharmacokinetics of digoxin which have a direct impact on its efficacy and toxicity profile. The developmental pharmacokinetics of the drug have been extensively studied such that profiles for age-dependent differences in the apparent volume of distribution, plasma and renal clearance and elimination half-life now exist. It is these data which have also produced the current age-specific dosing guidelines for the therapeutic administration of digoxin in various paediatric subpopulations. Despite this new knowledge, both accidental and iatrogenic digoxin toxicity still occurs in paediatric patients, with potentially life-threatening arrhythmias being produced when steady-state serum digoxin concentrations exceed 5.1 nmol/L. Consequently, the clinician may be faced with the decision to use antidotal therapy with digoxin-specific Fab fragments (d-Fab). This article reviews the developmental basis for digoxin disposition and its pharmacological and toxic effects. Additionally, the treatment of acute digoxin toxicity in children is reviewed, especially as pertains to the therapeutic use of d-Fab.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adair RF, Hellerstein HK, White LW. Digoxin induced exercise ECG changes in young men: ST-T walk through phenomenon above 80% max heart rate. Abstract. Circulation 45 & 46 (Suppl. II): 11, 1972

    Google Scholar 

  • Andersson KE, Bertler A, Wettrell G. Post-mortem distribution and tissue concentrations of digoxin in infants and adults. Acta Paediatrica Scandinavica 64: 497–504, 1975

    PubMed  CAS  Google Scholar 

  • Aronson JK. Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. Clinical Pharmacokinetics 8: 155–178, 1983

    PubMed  CAS  Google Scholar 

  • Aronson JK, Grahame-Smith DG. Monitoring digoxin therapy: II. Determinants of the apparent volume of distribution. British Journal of Clinical Pharmacology 4: 223–227, 1977

    PubMed  CAS  Google Scholar 

  • Asplund J, Edhag O, Mogensen L, Nyquist O, Orinius E, et al. Four cases of massive digitalis poisoning. Acta Medica Scandinavica 189: 293–297, 1971

    PubMed  CAS  Google Scholar 

  • Beermann B, Hellström K, Rosén A. The absorption of orally administered [12α-3H] digoxin in man. Clinical Science 43: 507–518, 1972

    PubMed  CAS  Google Scholar 

  • Beller GA, Smith TW, Abelmann WH, Haber E, Hood Jr WB. Digitalis intoxication: a prospective clinical study with serum level correlations. New England Journal of Medicine 284: 989–997, 1971

    PubMed  CAS  Google Scholar 

  • Berman WJ, Dubrynsky O, Whitman V, Friedman Z, Maisels MJ, et al. Digoxin therapy in low-birth-weight infants with patent ductus arteriosus. Pediatrics 93: 652–655, 1978

    Google Scholar 

  • Berman WJ, Ravenscroft PJ, Sheiner LB, Hemann MA, Melmon KL, et al. Differential effects of digoxin at comparable concentrations in tissues of fetal and adult sheep. Circulation Research 41: 635–642, 1977

    PubMed  CAS  Google Scholar 

  • Boldy DAR, Buckley BM, Vale JA. Advances in the treatment of poisoning I. Journal of Clinical Hospital Pharmacy 9: 147–160, 1984

    CAS  Google Scholar 

  • Bova S, Blaustein MP, Ludens JH, Harris DW, DuCharme DW, et al. Effects of an endogenous ouabain-like compound on heart and aorta. Hypertension 17: 944–950, 1991

    PubMed  CAS  Google Scholar 

  • Butler VP. Antibodies as specific antagonists of toxins, drugs and hormones. Pharmacology Review 34: 109–114, 1982

    CAS  Google Scholar 

  • Cappuccio FP, Markandu ND, Sagnella G, MacGregor GA. The effect of oral digoxin on sodium excretion, renin-angiotensin-aldosterone system and blood pressure in normotensive subjects. Postgraduate Medical Journal 62: 265–268, 1986

    PubMed  CAS  Google Scholar 

  • Clifton GD, McIntyre WJ, Zannikos PN, Harrison MR, Chandler MHH. Free and total serum digoxin concentrations in a renal failure patient after treatment with digoxin immune Fab. Journal of Clinical Pharmacology 8: 441–445, 1989

    CAS  Google Scholar 

  • Cokkinos DV, Tsartsalis GD, Heimonas ET, Gardikas CD. Comparison of the inotropic action of digitalis and isoproterenol in younger and older individuals. American Heart Journal 100: 802–806, 1980

    PubMed  CAS  Google Scholar 

  • Cusak B, Kelly J, O’Malley K, Noel J, Lavan J, et al. Digoxin in the elderly: pharmacokinetic consequences of old age. Clinical Pharmacology and Therapeutics 24: 772–776, 1979

    Google Scholar 

  • Dungan WT, Doherty JE, Harvey C, Char F, Dalrymple GV. Tritiated digoxin XVIII: studies in infants and chidren. Circulation 46: 983–988, 1972

    PubMed  CAS  Google Scholar 

  • Durakovic Z, Vrhovac B, Plavsic F. Electrocardiogram and high plasma digoxin concentration. International Journal of Clinical Pharmacology Therapy and Toxicology 22: 45–47, 1984

    CAS  Google Scholar 

  • Ebara H, Suzuke S, Nagashima K, Shimano S, Kuroume T. Digoxin-like immunoreactive substances in urine and serum from preterm and term infants: relationship to renal excretion of sodium. Journal of Pediatrics 108: 760–762, 1986

    PubMed  CAS  Google Scholar 

  • Ellenhorn MJ, Barceloux DG (Eds). Digoxin in medical toxicology: diagnosis and treatment of human poisoning, pp. 200–207, Elsevier, New York, 1988

    Google Scholar 

  • Erdmann E, Brown L. The cardiac glycoside-receptor system in the human heart. European Heart Journal 4(suppl. A): 61–65, 1983

    PubMed  CAS  Google Scholar 

  • Fisch C. Digitalis intoxication. Journal of the American Medical Association 216: 1770–1773, 1971

    PubMed  CAS  Google Scholar 

  • Ford AR, Aronson JK, Grahame-Smith DG, Carver JG. Changes in cardiac glycoside receptor sites, 86-rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phase of treatment of cardiac failure in regular rhythm and in atrial fibrillation. British Journal of Clinical Pharmacology 8: 125–134, 1979

    PubMed  CAS  Google Scholar 

  • Fowler RS, Rathi L, Keith JD. Accidental digitalis intoxication in children. Journal of Pediatrics 64: 188–200, 1964

    PubMed  CAS  Google Scholar 

  • Gault H, Vasdev S, Vlasses P, Longerich L, Dawe M. Interpretation of serum digoxin values in renal failure. Clinical Pharmacology and Therapeutics 39: 530–536, 1986

    PubMed  CAS  Google Scholar 

  • Glynn IM. The action of cardiac glycosides on ion movements. Pharmacological Reviews 16: 381–407, 1964

    PubMed  CAS  Google Scholar 

  • Goldring D. Withering’s account of foxglove and its use in children. Pediatrics 51: 549–550, 1973

    PubMed  CAS  Google Scholar 

  • Gorelick DA, Kussin SZ, Kahn I. Paranoid delusions and auditory hallucinations associated with digoxin intoxication. Journal of Nervous and Mental Disease 166: 817–819, 1978

    PubMed  CAS  Google Scholar 

  • Gorodischer R, Krasner J, Yaffe SJ. Serum protein binding of digoxin in newborn infants. Research Communications in Chemistry Pathology and Pharmacology 9: 387–390, 1974

    CAS  Google Scholar 

  • Gorodischer R, Jusko WJ, Sumner JY. Tissue and erythrocyte distribution of digoxin in infants. Clinical Pharmacology and Therapeutics 19: 256–263, 1976

    PubMed  CAS  Google Scholar 

  • Graves SW, Valdes R, Brown DA, Knight AB, Craig HR. Endogenous digoxin-immunoreactive substance in human pregnancies. Clinical Endocrinology and Metabolism 58: 740–751, 1984

    Google Scholar 

  • Greenblatt DJ, Duhme DW, Loch-Weser J, Smith TW. Bioavailability of digoxin tabalets and elixir in the fasting and postprandial states. Clinical Pharmacology and Therapeutics 16: 444.448, 1974

    PubMed  Google Scholar 

  • Greenwood H, Howard M, Landon J, Fraser B, Shinebourne E. Development of a highly sensitive radioimmunoassay for digoxin and its application in pediatric practice. European Journal of Cardiology 5: 413–424, 1977

    PubMed  CAS  Google Scholar 

  • Guthrie Jr GP. Effects of digoxin on responsiveness to the pressor actions of angiotensin and norepinephrine in man. Journal of Clinical Endocrinology and Metabolism 58: 76–80, 1984

    PubMed  CAS  Google Scholar 

  • Halkin H, Radomsky M, Blieden L, Frand M, Millman P, et al. Steady state serum digoxin concentration in relation to digitalis toxicity in neonates and infants. Pediatrics 61: 184–188, 1978

    PubMed  CAS  Google Scholar 

  • Harris MM, Hariprasad MD, Khalid S. Asymptomatic digoxin toxicity. New England Journal of Medicine 305: 643, 1981

    PubMed  CAS  Google Scholar 

  • Hastreiter AR, van der Horst RL, Chow-Tung E. Digitalis toxicity in infants and children. Pediatric Cardiology 5: 131–148, 1984

    PubMed  CAS  Google Scholar 

  • Hauck AJ, Ongley PA, Nadas AS. The use of digoxin in infants and children. American Heart Journal 56: 443–457, 1958

    PubMed  CAS  Google Scholar 

  • Hayes CJ, Butler VP, Gersony WM. Serum digoxin studies in infants and children. Pediatrics 52: 561–568, 1973

    PubMed  CAS  Google Scholar 

  • Hoffman BF, Bigger Jr JT. Digitalis and allied cardiac glycosides. In Gilman et al. (Eds) The pharmacological basis of therapeutics, 8th ed., pp. 814–827, Pergamon Press, New York, 1990

    Google Scholar 

  • Hubert U, Genz T, Reinhardt D. Comparison of the serum protein binding of digoxin in premature and mature newborns, infants, and adults. Biological Research in Pregnancy 6: 118–120, 1985

    CAS  Google Scholar 

  • Hursting MJ, Raisys VA, Opheim KE, Bell JL, Trobaugh GB, et al. Determination of free digoxin concentrations in serum for monitoring Fab treatment of digoxin overdose. Clinical Chemistry 33: 1652–1655, 1987

    PubMed  CAS  Google Scholar 

  • Johnson GL, Desai NS, Pauly TH, Cunningham MD. Complications associated with digoxin therapy in low-birth-weight infants. Pediatrics 69: 463–465, 1982

    PubMed  CAS  Google Scholar 

  • Joos HA, Johnson JL. Digitalis intoxication in infancy and childhood. Pediatrics 20: 866–876, 1957

    PubMed  CAS  Google Scholar 

  • Kearin M, Kelly JG, O’Malley K. Digoxin ‘receptors’ in neonates: an explanation of less sensitivity to digoxin than in adults. Clinical Pharmacology and Therapeutics 28: 346–349, 1980

    PubMed  CAS  Google Scholar 

  • Kearns GL, Moss MM, Clayton BD, Hewett DD. Pharmacokinetics and efficacy of digoxin specific Fab fragments in a child following massive digoxin overdose. Journal of Clinical Pharmacology 29: 901–908, 1989

    PubMed  CAS  Google Scholar 

  • Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children: a reappraisal. Clinical Pharmacokinetics 17(suppl.1): 29–67, 1989

    PubMed  Google Scholar 

  • Keller F, Kreutz G, Vöhringer H-F, Offermann G, Distler A. Effect of plasma exchange on the steady-state kinetics of digoxin and digitoxin. Clinical Pharmacokinetics 10: 514–523, 1985

    PubMed  CAS  Google Scholar 

  • Kim PW, Krasula RW, Soyka LF, Hastreiter AR. Postmortem tissue digoxin concentrations in infants and children. Circulation 52: 1128–1131, 1975

    PubMed  CAS  Google Scholar 

  • Koren G. Interaction between digoxin and commonly coadministered drugs in children. Pediatrics 75: 1032–1037, 1985

    PubMed  CAS  Google Scholar 

  • Koren G, Long D, Klein J, Beatie D, Bologacampeanu M, et al. Comparison of the digitalis receptor in erythrocytes from preterm infants and adults. Pediatric Research 23: 414–417, 1988

    PubMed  CAS  Google Scholar 

  • Krasula R, Yanagi R, Hastreiter AR, Levitsky S, Soyka LF. Digoxin intoxication in infants and children: correlation with serum levels. Journal of Pediatrics 84: 265–269, 1974

    PubMed  CAS  Google Scholar 

  • Kuschinsky K, Lahrtz H, Lullmann H, van Zwieten PA. Accumulation and release of 3H-digoxin by guinea pig heart muscle. British Journal of Pharmacology 30: 317–328, 1967

    CAS  Google Scholar 

  • Lang D, von Bernuth G. Serum concentration and serum half-life of digoxin in premature and mature newborns. Pediatrics 59: 902–906, 1977

    PubMed  CAS  Google Scholar 

  • Larbig D, Raff U, Haasis R. Reversal of digitalis effects by specific antibodies. Pharmacology 18: 1–8, 1979

    PubMed  CAS  Google Scholar 

  • Lewander WJ, Gaudreault P, Einhorn A, Henretig FM, Lacouture PG, et al. Acute pediatric digoxin ingestion, a ten year experience. American Journal of Diseases of Children 140: 770–773, 1986

    PubMed  CAS  Google Scholar 

  • Linday LA, Dobkin JF, Wang TC, Butler VP, Saha JR, et al. Digoxin inactivation by the gut flora in infancy and childhood. Pediatrics 79: 544–548, 1987

    PubMed  CAS  Google Scholar 

  • Linday LA, Drayer DE, Ali Khan MA, Cicalese C, Reidenberg MM. Pubertal changes in net renal tubular secretion of digoxin. Clinical Pharmacology and Therapeutics 35: 438–446, 1984

    PubMed  CAS  Google Scholar 

  • Litovitz TL, Norman SA, Veltri JC. 1985 Annual report of the American Association of Poison Control Centers national data collection system. American Journal of Emergency Medicine 4: 427–458, 1986

    PubMed  CAS  Google Scholar 

  • Loes MW, Singh S, Lock JE, Mirkin BL. Relation between plasma and red-cell electrolyte concentrations and digoxin levels in children. New England Journal of Medicine 299: 501–504, 1978

    PubMed  CAS  Google Scholar 

  • Ludens JH, Clark MA, DuCharme DW, Harris DW, Lutzke BS, et al. Purification of an endogenous digitalis-like factor from human plasma for structural analysis. Hypertension 17: 923–929, 1991

    PubMed  CAS  Google Scholar 

  • Marban E, Smith TW. Digitalis. In Fozzard et al. (Eds) The heart and cardiovascular system, pp. 1573–1596, Raven Press, New York, 1986

    Google Scholar 

  • Martiny SS, Phelps SJ, Massey KL. Treatment of severe digitalis intoxication with digoxin-specific antibody fragments: a clinical review. Critical Care Medicine 16: 629–635, 1988

    PubMed  CAS  Google Scholar 

  • Mathews WR, DuCharme DW, Hamlyn JM, Harris DW, Mandel F, et al. Mass spectral characterization of an endogenous digitalis-like factor from human plasma. Hypertension 17: 930–935, 1991

    PubMed  CAS  Google Scholar 

  • Mooradian AD. Digitalis: an update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations. Clinical Pharmacokinetics 15: 165–179, 1988

    PubMed  CAS  Google Scholar 

  • Morgan JP, Chesebro JH, Pluth JR, Puga RJ, Schaff HV. Intracellular calcium transients in human working myocardium as detected with aequorin. Journal of the American College of Cardiology 3: 410–417, 1984

    PubMed  CAS  Google Scholar 

  • Morselli PL. Clinical pharmacology of the perinatal period and early infancy. Clinical Pharmacokinetics 17(suppl. 1): 13–28, 1989

    PubMed  Google Scholar 

  • Murphy DJ, Bremner WF, Haber E, Butler VP, Smith TW, et al. Massive digoxin poisoning treated with Fab fragments of digoxin-specific antibodies. Pediatrics 70: 472–473, 1982

    PubMed  Google Scholar 

  • Nadas AS, Rudolph AM, Reinhold JD. The use of digitalis in infants and children. New England Journal of Medicine 248: 98–105, 1953

    PubMed  CAS  Google Scholar 

  • Nollet H, Verhaaren H, Stroobandt R, Belpaire F. Delayed elimination of digoxin antidotum determined by radioimmunoassay. Journal of Clinical Pharmacology 29: 41–45, 1989

    PubMed  CAS  Google Scholar 

  • Ordog GJ, Benaron S, Bhasin V, Wasserberger J, Balasubramaniam S. Serum digoxin levels and mortality in 5,100 patients. Annals of Emergency Medicine 16: 32–39, 1987

    PubMed  CAS  Google Scholar 

  • Park MK, Ludden T, Arom KV, Rogers J, Oswalt JD. Myocardial vs serum digoxin concentrations in infants and adults. American Journal of Diseases of Children 136: 418–420, 1982

    PubMed  CAS  Google Scholar 

  • Pearce G, Buchanan N, Uther J. Massive digoxin ingestion in a child. Medical Journal of Australia 2: 279–280, 1980

    PubMed  CAS  Google Scholar 

  • Platt D, Schock P. Effect of age and cardiac glycosides on the activity of adenosine triphosphatase (ATPase) of red cell ghost membranes. Mechanisms of Aging and Development 3: 245–262, 1974

    CAS  Google Scholar 

  • Powell AC, Horowitz JD, Hasin Y, Syrjanen ML, Horomidis S, et al. Acute myocardial uptake of digoxin in humans: correlation with hemodynamic and electrocardigraphic effects. Journal of the American College of Cardiology 15: 1238–1247, 1990

    PubMed  CAS  Google Scholar 

  • Pudek MR, Seccombe DW, Jacobson BE, Whitfield MF. Seven different digoxin immunoassay kits compared with respect to interference by a digoxin-like immunoreactive substance in serum from premature and fullterm infants. Clinical Chemistry 29: 1972–1974, 1983

    PubMed  CAS  Google Scholar 

  • Rane A, Wilson JT. Clinical pharmacokinetics in infants and children. Clinical Pharmacokinetics 1: 2–24, 1976

    PubMed  CAS  Google Scholar 

  • Rietbrock N, Alken RG. Color vision deficiencies: a common sign of intoxication in chronically digoxin-treated patients. Journal of Cardiovascular Pharmacology 2: 93–99, 1980

    PubMed  CAS  Google Scholar 

  • Roberts RJ. Cardiovascular drugs. In Roberts (Ed.) Pharmacologic principles and clinical experience, pp. 138–156, W.B. Saunders, Philadelphia, 1984

    Google Scholar 

  • Rodin SM, Johnson BF. Pharmocokinetic interactions with digoxin. Clinical Pharmacokinetics 15: 227–244, 1988

    PubMed  CAS  Google Scholar 

  • Rose SR, Gorman RL, McDaniel J. Fatal digoxin poisoning: an unsuccessful resuscitation with use of digoxin-immune Fab. American Journal of Emergency Medicine 5: 509–511, 1987

    PubMed  CAS  Google Scholar 

  • Rosen KG, Sigstron L. The influence of age on Na+,K+-ATPase activity in erythrocytes in fetal and newborn guinea pigs. Journal of Perinatal Medicine 6: 154–159, 1978

    PubMed  CAS  Google Scholar 

  • Rossi R, Leititis JU, Hagel KJ, Smolarz A, Brandis M. Severe digoxin intoxication in a child treated by infusion of digoxin-specific Fab-antibody fragments. European Journal of Pediatrics 142: 138–140, 1984

    PubMed  CAS  Google Scholar 

  • Rutledge J. Digitalis toxicity in infants and plasma digoxin levels. Pediatric Cardiology 6: 51, 1985

    PubMed  CAS  Google Scholar 

  • Schaumann W, Kaufmann B, Neubert P, Smolarz A. Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. European Journal of Clinical Pharmacology 30: 527–533, 1986

    PubMed  CAS  Google Scholar 

  • Senger TL, Butler VP, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. Journal of the American College of Cardiology 5: 118A–123A, 1985

    Google Scholar 

  • Sherron PA, Gelband H. Case study: reversal of digoxin toxicity with Fab fragments in a pediatric patient with acute renal failure. In Management of digitalis toxicity: the role of DIGI-BIND, pp. 50–54, Burroughs Wellcome Co., Research Triangle Park, 1986

    Google Scholar 

  • Shumaik GM, Wu AW, Ping AC. Oleander poisoning: treatment with digoxin-specific Fab antibody fragments. Annals of Emergency Medicine 17: 732–735, 1988

    PubMed  CAS  Google Scholar 

  • Smith TW. Digitalis: mechanisms of action and clinical use. New England Journal of Medicine 318: 358–365, 1988

    PubMed  CAS  Google Scholar 

  • Smith TW, Butler VP, Haber E, Fozzard H, Marcus FI, et al. Treatment of life-treatening digitalis intoxication with digoxin-specific Fab antibody fragments: experience in 26 cases. New England Journal of Medicine 307: 1357–1362, 1982

    PubMed  CAS  Google Scholar 

  • Smith TW, Haber E, Yeatman L, Butler VP. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. New England Journal of Medicine 294: 797–800, 1976

    PubMed  CAS  Google Scholar 

  • Smolarz A, Roesch E, Lenz E, Neubert H, Abshagen P. Digoxin specific antibody (Fab) fragments in 34 cases of severe digitalis intoxication. Clinical Toxicology 23: 327–340, 1985

    PubMed  CAS  Google Scholar 

  • Springer M, Olson KR, Feaster W. Acute massive digoxin overdose: survival without use of digitalis-specific antibodies. American Journal of Emergency Medicine 4: 364–368, 1986

    PubMed  CAS  Google Scholar 

  • Stone J, Bentur Y, Zalstein E, Soldin S, Giesbrecht E, et al. Effect of endogenous digoxin-like substances on the interpretation of high concentrations of digoxin in children. Journal of Pediatrics 117: 321–325, 1990

    PubMed  CAS  Google Scholar 

  • Sullivan JB. Immunotherapy in the poisoned patient: overview of present applications and future trends. Medical Toxicology 1: 47–60, 1986

    PubMed  Google Scholar 

  • Sundqvist K, Atterhog JH, Jogestrand T. Effect of digoxin on the electrocardiogram at rest and during exercise in healthy subjects. American Journal of Cardiology 57: 661–665, 1986

    PubMed  CAS  Google Scholar 

  • Sweadner KJ, Goldin SM. Active transport of sodium and potassium ions: mechanism, function, and regulation. New England Journal of Medicine 302: 777–783, 1980

    PubMed  CAS  Google Scholar 

  • Tonkon MJ, Lee G, DeMaria AN, Miller RR, Mason DT. Effects of digitalis on the exercise electrocardiogram in normal adult subjects. Chest 72: 714–718, 1977

    PubMed  CAS  Google Scholar 

  • Valdes R, Graves SW, Brown BA, Landt M. Endogenous substance in newborn infants causing false positive digoxin measurements. Journal of Pediatrics 102: 947–950, 1983

    PubMed  CAS  Google Scholar 

  • Wagner JG, Dick M, Behrendt DM, Lockwood GF, Sakmar E, et al. Determination of myocardial and serum digoxin concentrations in children by specific and non-specific assay methods. Clinical Pharmacology and Therapeutics 33: 577–584, 1983

    PubMed  CAS  Google Scholar 

  • Wettrell G. Distribution and elimination of digoxin in infants. European Journal of Clinical Pharmacology 11: 329–335, 1977

    PubMed  CAS  Google Scholar 

  • Wettrell G, Andersson KE. Clinical pharmacokinetics of digoxin in infants. Clinical Pharmacokinetics 2: 17–31, 1977

    PubMed  CAS  Google Scholar 

  • Wettrell G, Andersson KE. Cardiovascular drugs II: digoxin. Therapeutic Drug Monitoring 8: 129–139, 1986

    PubMed  CAS  Google Scholar 

  • Wettrell G, Andersson KE, Bertler A, Lundstrom NR. Concentrations of digoxin in plasma and urine in neonates, infants and children with heart disease. Acta Paediatrica Scandinavica 63: 705–710, 1974

    PubMed  CAS  Google Scholar 

  • Wettrell G, Andersson KE, Nyberg L. Effect of exchange transfusion on the elimination of digoxin in neonates. European Journal of Clinical Pharmacology 10: 25–29, 1976

    Google Scholar 

  • Wolach B, Carmi D, Shilo L, Dolev S, Shenkman L. Endogenous digoxin-like factor in neonates: effect of age and relation to serum bilirubin levels. Acta Paediatrica Scandinavica 78: 364–368, 1989

    PubMed  CAS  Google Scholar 

  • Yatscoff RW, Desjardins PRE, Dalton JG. Digoxin-like immunoreactivity in the serum of neonates and uremic patients as measured in the Abbott TDX. Clinical Chemistry 30: 588, 1984

    PubMed  CAS  Google Scholar 

  • Zucker AR, Lacina SJ, DasGupta DS, Fozzard HA, Mehlman D, et al. Fab fragments of digoxin-specific antibodies used to reverse ventricular fibrillation induced by digoxin ingestion in a child. Pediatrics 70: 468–471, 1982

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Thomas G. Wells &  Gregory L. Kearns

  2. Division of Pediatric Clinical Pharmacology, Arkansas Children’s Hospital, Little Rock, Arkansas, USA

    Thomas G. Wells, Ronald A. Young &  Gregory L. Kearns

  3. Division of Pediatric Nephrology, Arkansas Children’s Hospital, Little Rock, Arkansas, USA

    Thomas G. Wells

  4. Department of Pharmacy Services, Arkansas Children’s Hospital, Little Rock, Arkansas, USA

    Ronald A. Young

Authors
  1. Thomas G. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald A. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregory L. Kearns
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wells, T.G., Young, R.A. & Kearns, G.L. Age-Related Differences in Digoxin Toxicity and its Treatment. Drug-Safety 7, 135–151 (1992). https://doi.org/10.2165/00002018-199207020-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199207020-00005

Keywords

Search

Navigation