Monitoring: Obtain blood samples at least 4 hrs after IV dose and 6-8hrs after an oral dose. Serum levels: 0.5 to 2.0 ng/ml. Obtain the first level within 24 hours of digitalization. Monitor BUN and serum creatinine q2days (qd if unstable). Monitor apical pulse daily. Onset/peak: IV: 5-30min/ 1-4hrs Oral: 1-2hrs/ 2-8 hrs. Time to steady state: 5-7 days (average) ESRD: 15-20 days. Half-life: 38-48 hrs. (anephric: 4-6 days).
Factors that increase the likelihood of digoxin toxicity: Hypokalemia, hypomagnesemia, hypothyroidism, renal dysfunction, interacting drugs (eg quinidine, verapamil).
Distribution: only a small fraction of digoxin in present in the blood (little is removed by hemodialysis). Digoxin distributes very little into body fat–doses must be based on lean body weight. Distribution is not altered by obesity. There appears to be a gradual contraction in the volume of distribution as renal function deteriorates. Therefore, extreme caution is necessary when dosing patients with renal failure.
Maximal response from any maintenance dose of digoxin will be obtained when serum concentrations are at steady state and maximal body stores for that dose have been obtained. It should be noted that any adjustment of dose or change in the elimination of digoxin requires a waiting period of 4-5 times the half-life (1 week with normal renal function) before the new steady state concentration is achieved.
Aronson JK: Clinical pharmacokinetics of cardiac glycosides in
patients with renal dysfunction. Clin Pharmacokinet 1983; 8:155-178.
Behr ER, Veysey MJ, Berry D, Volans GN. Optimum dose of
digoxin. Lancet. 1997 Jun 21;349(9068):1845
Bennett WM, Aronoff GR, Golper TA et al: Drug Prescribing in Renal
Failure. American College of Physicians, Philadelphia, PA, 1987.
Cauffield JS, Gums JG, Grauer K. The serum digoxin concentration:
ten questions to ask. Am Fam Physician. 1997 Aug;56(2):495-503,
Cheng JW, Charland SL, Shaw LM, Kobrin S, Goldfarb S, Stanek EJ,
Spinler SA. Is the volume of distribution of digoxin reduced
in patients with renal dysfunction? Determining digoxin
pharmacokinetics by fluorescence polarization immunoassay.
Pharmacotherapy. 1997 May-Jun;17(3):584-90.
Fenster PE, Hager WD & Goodman MM: Digoxin-quinidine-spironolactone
interaction. Clin Pharmacol Ther 1984; 36:70-73.
Gilman AG, Rall TW, Nies AS et al (Eds): Goodman and Gilman's The
Pharmacological Basis of Therapeutics, 8th ed. Macmillan Publishing
Co, New York, NY, 1990.
Hammerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic
and pharmacodynamic changes in the elderly. Clinical implications.
Clin Pharmacokinet. 1998 Jul;35(1):49-64.
Hui J, Wang YM, Chandrasekaran A, Geraets DR, Caldwell JH, Robertson
LW, Reuning RH. Disposition of tablet and capsule formulations
of digoxin in the elderly. Pharmacotherapy. 1994
Jelliffe, 1968; Product information Lanoxin (R), Glaxo Wellcome Inc.
(Jelliffe RW: An improved method digoxin therapy. Ann Intern Med
Jusko WJ, Szefler SJ & Goldfarb AL: Pharmacokinetic design of
digoxin dosage regimens in relation to renal function. J Clin
Pharmacol, 1974; 14:525-535.
Koda-Kimble MA: Congestive heart failure, in Applied Therapeutics
for Clinical Pharmacists, 2nd ed, edited by Koda-Kimble et al,
Applied Therapeutics, Inc., San Francisco 1978; pp 161-86.
Kramer WG, Lewis RP, Cobb TC et al: Pharmacokinetics of digoxin:
comparison of a two and a three compartment model in man. J
Pharmacokinet Biopharm 1974; 2:299.
Lee CH, Park YJ, Sands CD, Jones DW, Trang JM.
Bioavailability of digoxin tablets in healthy volunteers. Arch
Pharm Res. 1994 Apr;17(2):80-6.
Mooradian AD: Digitalis: An update of clinical pharmacokinetics,
therapeutic monitoring techniques and treatment recommendations.
Clin Pharmacokinet 1988; 15:165-179.