Summary
The correct loading dose of digoxin in patients with advanced renal failure is still a matter of discussion. The effect has been studied of loading doses of digoxin 0.625 mg or 1.25 mg given over 48 h according to randomized crossover design to healthy volunteers and to two different groups of patients with renal impairment and the same mean endogenous creatinine clearance of about 15 ml/min. The subsequent maintenance dose for 4 days was digoxin 0.25 mg in the volunteers and 0.125 mg in both groups of patients. The minimum plasma digoxin concentrations before each dose was measured by radioimmunoassay and the plasma levels in the different groups have been compared. In the healthy volunteers no significant difference was found during the study, despite wide variation in the plasma digoxin concentration. In contrast, in patients with renal failure, the group with the higher loading dose showed significantly higher plasma concentrations 24, 36 and 48 h after drug administration, reaching the highest mean value of 2.2 ng/ml at 48 h. However, after 120 h of maintenance therapy a mean digoxin concentration of 1.3 mg/ml was found in both groups. Thus, despite different loading doses identical plasma concentrations were reached during administration of the same maintenance therapy. The higher plasma digoxin concentration obtained during administration of a higher loading dose might be the cause of arrythmias in individual patients.
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References
Beveridge T, Nüesch E, Ohnhaus EE (1978) Absolute bioavailability of digoxin tablets. Arzneim Forsch (Drug Res) 28: 701–703
Chamberlain DA, White RJ, Howard MR, Smith TW (1970) Plasma digoxin concentrations in patients with atrial fibrillation. Br Med J 3: 429–432
Chung EK (1969) Digitalis intoxication. Williams and Wilkins, Baltimore, pp 1–2
Dengler HJ, Bodem G, Wirth K (1973) Pharmacokinetic and metabolic studies with lanhatoside C, α- and β-acetyldigoxin and digoxin in man. Pharmacology and the future of man. Proc 5th Int Congr Pharmacology San Francisco 1972, Vol 3. Karger, Basel, pp 112–126
Evered DC, Chapman C (1971) Plasma digoxin concentrations and digoxin toxicity in hospital patients. Br Heart J 33: 540–545
Greenblatt DJ, Smith TW, Koch-Weser J (1976) Bioavailability of drugs/ the digoxin dilemma. Clin Pharmacokinet 1: 36–51
Jeliffe RW (1968) An improved method of digoxin therapy. Ann Intern Med 69: 703–717
Johnston GD, Harron WG, McDevitt DG (1979) Can digoxin prescribing be improved? A comparison between intuitive and assisted dose selection. Eur J Clin Pharmacol 16: 229–235
Koup JR, Greenblatt DJ, Jusko WJ, Smith TW, Koch-Weser J (1975a) Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. J Pharmacokinet Biopharm 3: 181–192
Koup JR, Jusko WJ, Elwood CM, Kohli RK (1975b) Digoxin Pharmacokinetics: Role of renal failure in dosage regimen design. Clin Pharmacol Ther 18: 9–21
Nyberg L, Anderson KE, Bertler A (1974) Bioavailability of digoxin from tablets: II. Radioimmunoassay and disposition pharmacokinetics of digoxin after intravenous administration. Acta Pharm Suec 2: 459–470
Ohnhaus EE, Vozeh S, Nüesch E (1979a) Absorption of digoxin in severe right heart failure. Eur J Clin Pharmacol 15: 115–120
Ohnhaus EE, Vozeh S, Nüesch E (1979b) Absolute bioavailability of digoxin in chronic renal failure. Clin Nephrol 11: 302–306
Rabkin SW, Grupp G (1975) A two compartment open model for digoxin pharmacokinetics in patients receiving a wide range of digoxin doses. Acta Cardiol 30: 343–351
Reuning RH, Sams RA, Notari RE (1973) Role of pharmacokinetics in drug dosage adjustment. I. Pharmacologie effect kinetics and apparent volume of distribution. J Clin Pharmacol 13: 127–141 (1973)
Sachs L (1978) Angewandte Statistik. Springer, Berlin Heidelberg New York
Wagner JG (1974) Loading and maintenance doses of digoxin in patients with normal renal function and those with severly impaired renal function. J Clin Pharmacol 14: 329–338
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Ohnhaus, E.E., Lenzinger, H.R. & Galeazzi, R.L. Comparison of two different loading doses of digoxin in severe renal impairment. Eur J Clin Pharmacol 18, 467–472 (1980). https://doi.org/10.1007/BF00874657
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DOI: https://doi.org/10.1007/BF00874657