Clinical and Pharmacokinetic Profiles of Digoxin Immune Fab in Four Patients with Renal Impairment

Allen, Nancy M.; Dunham, Gary D.; Sailstad, Jeffrey; Findlay, J. W. A.

doi:10.1177/106002809102501205

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…In contrast, Ujhelyi and associates (26) documented redevelopment of digoxin toxicity in 3 of 14 patients (21 %) with renal dysfunction. Others have documented a rebound in free serum digoxin concentration after administra- tion of FAB in patients with renal dysfunction (27,28) without the development of recurrent toxicity. The magnitude of this rebound is unpredictable (28) and, although it rarely exceeds the therapeutic range of digoxin (26), it may place patients at risk for rebound toxicity, particularly those with renal dysfunction.…”

Section: Discussionmentioning

confidence: 97%

“…Others have documented a rebound in free serum digoxin concentration after administra- tion of FAB in patients with renal dysfunction (27,28) without the development of recurrent toxicity. The magnitude of this rebound is unpredictable (28) and, although it rarely exceeds the therapeutic range of digoxin (26), it may place patients at risk for rebound toxicity, particularly those with renal dysfunction. This point should be underscored because we are suggesting the more aggressive use of FAB in patients with non-life-threatening digoxin toxicity and concomitant renal impairment.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Analysis of the Use of Digoxin Immune Fab for the Treatment of Non-Life-Threatening Digoxin Toxicity

DiDomenico

Walton

Sanoski

et al. 2000

J Cardiovasc Pharmacol Ther

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Analysis of the Use of Digoxin Immune Fab for the Treatment of Non-Life-Threatening Digoxin Toxicity

DiDomenico

Walton

Sanoski

et al. 2000

J Cardiovasc Pharmacol Ther

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“…'~,*~ Free and total digoxin concentrations after Fab were assayed by two systems that have been described previously by our laborato-ries. 12,14,21,22 Three patient samples were analyzed by a fluorescence polarization immunoassay (TDx, Digoxin 11, Abbott Laboratories Diagnostic Division, Irving, Texas) that used kit standards, whereas samples from two patients were analyzed by use of an immunofluorometric assay (Pharmacia Diagnostics, Fairfield, N.J.).…”

Section: Methodsmentioning

confidence: 99%

Disposition of digoxin immune fab in patients with kidney failure

Ujhelyi

Robert

Cummings

et al. 1993

Clin Pharmacol Ther

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Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free digoxin were studied in five digoxin-toxic patients with end-stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (+/- SD) serum creatinine of 5.9 +/- 1.2 mg/dl (four patients were receiving long-term hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration-time profile of Fab appeared to be similar to the concentration-time profile of total digoxin. The mean (+/- SD) half-lives of the alpha and beta disposition phases of Fab were 13 +/- 5 hours and 96 +/- 31 hours, respectively, which were similar to the alpha and beta parameter estimates of total digoxin (14 +/- 4 and 123 +/- 16 hours, respectively). Steady-state volume of distribution and systemic clearance of Fab were 0.29 +/- 0.11 L/kg and 0.057 +/- 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total digoxin are markedly delayed in patients with end-stage renal disease, which may necessitate prolonged clinical monitoring.

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“…[7] These values are higher than the volume of distribution at steadystate (V ss) in patients with renal disease. [7,8] It is known, however, that V z commonly overpredicts the more appropriate volume of distribution term, V ss . Thus, it appears that moderate and severe renal impairment have no effect on the volume of distribution of Fab.…”

Section: 2 Pharmacokinetics In Patients With Renal Diseasementioning

confidence: 98%

“…1). [4,[7][8][9][10][11][12][13]20,[23][24][25][26][27][28][29][30] At the same time, there is a rapid decrease in the free fraction of digoxin in plasma from between 75 and 90% to between 0 and 5%.£4,7-13,20,23-30] Because the majority oftotal digoxin remains bound to Fab, the elimination of total digoxin becomes dependent on the disposition of Fab. [4,7-13,23 ,24] Thus, total digoxin also has a biexponential concentration-time profile.…”

Section: Pharmacokinetics Of Digoxin During Fab Therapymentioning

confidence: 99%

Pharmacokinetic Aspects of Digoxin-Specific Fab Therapy in the Management of Digitalis Toxicity

Ujhelyi

Robert

1995

Clinical Pharmacokinetics

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Digoxin intoxication occurs frequently and may require treatment with digoxin-specific Fab therapy. Little is known, however, regarding the biological fate of this compound. Pharmacokinetic studies have not been performed in healthy volunteers, but there are limited kinetic data from patients who have received therapy for the treatment of digoxin toxicity. Digoxin-specific Fab is eliminated via renal and nonrenal routes, having a volume of distribution slightly exceeding extracellular volume (0.40 L/kg) and an elimination half-life of 16 to 20 hours. Patients with renal impairment and end-stage renal disease have elimination half-life values that are prolonged up to 10-fold in magnitude, while volume of distribution is unaffected. Systemic clearance of digoxin-specific Fab is approximately 0.32 ml/min/kg in digoxin-toxic patients with preserved renal function. Renal failure also decreases Fab clearance by up to 75%. Therefore, Fab may reside in the serum of anephric patients for 2 to 3 weeks after administration. More important is the effect of Fab on the disposition of digoxin. Because digoxin-specific Fab has a stronger digoxin-binding affinity than do biological membranes, it can sequester tissue-bound and intracellular digoxin into the extracellular spaces. This results in a rapid increase in digoxin serum concentrations in the central compartment. Since the majority of digoxin is bound by Fab, it cannot interact with its biological receptor and thus reverses digoxin toxicity. The pharmacokinetic fate of total digoxin after administration of digoxin-specific Fab follows that of Fab. However, it appears that the elimination half-life of Fab is slightly shorter than that of total digoxin in patients with end-stage renal disease, suggesting that the clearance of Fab is slightly faster than that of total digoxin. Free digoxin concentrations fall rapidly after Fab administration and then rebound upwards within 12 to 24 hours. This rebound in free digoxin concentrations, however, is delayed by 12 to 130 hours in patients with renal dysfunction and end-stage renal disease. Rebound in free digoxin concentrations occurs during the initial phase of the biexponential decline of the serum concentration-time profile for digoxin-specific Fab, suggesting that distribution from the vascular spaces is the likely cause. Following the increase, free digoxin concentrations decline in a manner that is dependent on renal and nonrenal routes of elimination. During this time period it is evident that Fab retains it capability of binding digoxin while it resides in plasma. There is no evidence to support a dissociation between the Fab-digoxin complex over extended periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

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Clinical and Pharmacokinetic Profiles of Digoxin Immune Fab in Four Patients with Renal Impairment

Cited by 10 publications

References 12 publications

Analysis of the Use of Digoxin Immune Fab for the Treatment of Non-Life-Threatening Digoxin Toxicity

Analysis of the Use of Digoxin Immune Fab for the Treatment of Non-Life-Threatening Digoxin Toxicity

Disposition of digoxin immune fab in patients with kidney failure

Pharmacokinetic Aspects of Digoxin-Specific Fab Therapy in the Management of Digitalis Toxicity

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