Disposition of digitoxin in renal failure

Hf, Vöhringer; Rietbrock, N.; Spurny, P; Kuhlmann, J.; Hampl, H.; Baethke, R

doi:10.1002/cpt1976194387

Cited by 32 publications

(2 citation statements)

References 4 publications

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“…V ohringer and his colleagues (Vohringer and Rietbrock, 1974;Vohringer et al, 1976) found that the total urinary and faecal excretion of digitoxin was not altered in renal dysfunction but that the reduced renal excretion of digitoxin was compensated for by an increased faecal excretion. However, such a finding would suggest that there was no change in metabolism of digitoxin in renal dysfunction contrary to other evidence that digitoxin metabolism is altered.…”

Section: Urinary and Faecal Elimination Of Digitoxin And Its Metabolitesmentioning

confidence: 97%

Clinical Pharmacokinetics of Cardiac Glycosides in Patients with Renal Dysfunction

Aronson

1983

Clinical Pharmacokinetics

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The pharmacokinetics of different cardiac glycosides are altered by renal dysfunction in different ways, depending on their basic pharmacokinetic properties.Digoxin: The linearity of digoxin pharmacokinetics is unchanged by renal dysfunction, as is the bioavailability. Protein binding may be slightly reduced, but the change is of no clinical significance. The apparent volume of distribution is reduced by one-third to onehalf, the change being roughly proportional to the degree of renal impairment. The significance of this change in terms of adjustment of the loading dose is controversial. I believe that the initial oral loading dose should be reduced from 15 pg/kg to 10 pg/kg in renal dysfunction, and supplemented only if there is evidence of a lack of response and no evidence of toxicity.The renal clearance of digoxin is reduced in renal dysfunction and becomes very closely related to the measured creatinine clearance at values of creatinine clearance below 30 ml/ min. As a result, the renal elimination rate constant, and therefore the fraction of the total body load lost per day via the kidneys, falls in renal dysfunction. In contrast, the non-renal clearance of digoxin is probably unaffected. However, because of the fall in apparent volume of distribution the non-renal elimination rate constant rises slightly, accounting for the slight increase in faecally excre.ted digoxin in renal dysfunction. This rise in the non-renal fractional daily loss is not sufficient to counteract the fall in renal fractional daily loss and digoxin maintenance dosages at steady-state need to be reduced. For this purpose the creatinine clearance acts as an initial guide to the extent of the expected reduction in dose, but doses altered on this basis should be regarded as first approximations to the correct dose, and the dose subsequently readjusted according to the patient's clinical response, using the plasma digoxin concentration as a guide. It must be remembered, however, that because of technical problems with digoxin radioimmunoassay in renal dysfunction, and because of the difficulty in interpretation of the result, the plasma digoxin concentration in renal dysfunction is of less value than it is in normal renal function. The overall half-life of digoxin is prolonged in renal dysfunction and it therefore takes longer for a steady-state to be reached during maintenance dose therapy without a loading dose, and longer for toxicity, when it occurs, to resolve.Negligible amounts of digoxin are removed from the body by dialysis procedures. A transplanted kidney retains its ability to handle digoxin, and after transplantation the pharmacokinetics of digoxin return towards normal, depending on the overall improvement in renal function achieved.Digitoxin: There are technical problems with the measurement of digitoxin because of the need to separate digitoxin and its metabolites chromatographically before using the measurement techniques commonly applied. Such separation has not always been carried out, and this makes the interpretation ...

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Section: Urinary and Faecal Elimination Of Digitoxin And Its Metabolitesmentioning

confidence: 97%

Clinical Pharmacokinetics of Cardiac Glycosides in Patients with Renal Dysfunction

Aronson

1983

Clinical Pharmacokinetics

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“…These metabolites have been noted in the plasma of renal failure patients given digitoxin. 14 Digoxigenin-bis-digitoxoside and digoxigenin-rnono-digitoxoside are cardioactive': 3 and also bind to the digoxin antibody commonly used in the 125 1 digoxin radioimmunoassay (RIA), 12 On a molar basis, digoxigenin-bisdigitoxoside and digoxigenin-mono-digitoxoside crossreact with the digoxin antibody to the same degree as digoxin,"- 10 If metabolites of digoxin cumulate in the plasma of renal failure patients the apparent digoxin concentrations as measured by standard 125 1 RIA would be higher than those determined by a more specific assay, One consequence of this would be that the apparent volume of distribution of digoxin would be artifactually decreased in renal failure. This possibility has not been seriously considered in studies reporting that the volume of distribution of digoxin is reduced in renal failure.…”

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confidence: 99%

The question of cumulation of digoxin metabolites in renal failure

Gibson

Nelson

1980

Clin Pharmacol Ther

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Using high-performance liquid chromatography (HPLC) to separate digoxin from its metabolites digoxigenin, digoxigenin-bis-digitoxoside, and digoxigenin-mono-digitoxoside with subsequent quantitation by 125I radioimmunoassay (RIA), we examined the plasma of patients on long-term oral digoxin therapy. Digoxin was also measured by RIA without prior HPLC separation. Nine patients requiring maintenance dialysis and 9 subjects with lesser degrees of renal impairment were studied. Trace amounts of 1 or more of the digoxin metabolites were found in the plasma of all dialysis patients while subjects with lesser degrees of renal failure had either none or only 1 metabolite in trace amounts. The ratio of HPLC digoxin without HPLC was 0.83 +/- 0.12 (SD) in renal failure patients and 1.06 +/- 0.09 in subjects with renal function (p less than 0.01). RIA overestimates the amount of digoxin in plasma of renal failure patients and in them from 6% to 42% of plasma digoxin, as determined by conventional 125I RIA, may represent compounds other than digoxin.

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Enhanced Transformation of Digitoxin to Dihydrodigitoxin in Humans with Renal Failure

Bodem¹,

Unruh²

1979

The Journal of Clinical Pharma

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A gas-chromatographic mass-spectroscopic technique was used to identify dihydrodigitoxin, a metabolite of digitoxin, in the plasma of healthy volunteers and patients with renal failure. Digitoxin and dihydrodigitoxin were extracted from plasma and derivatized with heptafluorbutyric anhydride. In normal subjects, only minimal concentrations of dihydrodigitoxin in plasma could be determined (1 ng/ml) after an intravenous bolus injection of digitoxin. Under a chronic treatment with a daily dose of 0.1 mg digitoxin in three out of seven individuals, detectable dihydrodigitoxin plasma levels were observed (0.7, 1.5, and 1.7 ng/ml) (Table I). On the other hand, in seven patients with renal failure, high dihydrodigitoxin plasma concentrations (8.9 +/- 0.9 ng/ml) were shown which were in a similar range as those of the parent compound (8.7 +/- 2.2 ng/ml) under a maintenance treatment with digitoxin.

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Disposition of digitoxin in renal failure

Cited by 32 publications

References 4 publications

Clinical Pharmacokinetics of Cardiac Glycosides in Patients with Renal Dysfunction

Clinical Pharmacokinetics of Cardiac Glycosides in Patients with Renal Dysfunction

The question of cumulation of digoxin metabolites in renal failure

Enhanced Transformation of Digitoxin to Dihydrodigitoxin in Humans with Renal Failure

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