Influence of Digoxin Immune Fab Therapy and Renal Dysfunction on the Disposition of Total and Free Digoxin

  1. Michael R. Ujhelyi;
  2. Sylvie Robert;
  3. Doyle M. Cummings;
  4. Robert D. Colucci;
  5. Paul J. Green;
  6. Jeffrey Sailstad;
  7. Peter H. Vlasses; and
  8. Barbara J. Zarowitz
  1. From Hartford Hospital and University of Connecticut, Hartford and Storrs, Connecticut; College of Pharmacy, Henry Ford Hospital and Wayne State University, Detroit, Michigan; East Carolina University School of Medicine, Greenville, North Carolina; Jefferson Medical College, Philadelphia, Pennsylvania; University Hospital Consortium, Oak Brook, Illinois; Wellcome Research Laboratories, Research Triangle Park, North Carolina. Requests for Reprints: Michael R. Ujhelyi, PharmD, College of Pharmacy, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH 45267-0004. Grant Support: By Baxter Dade Healthcare Company. Acknowledgments: The authors thank Thomas L. Wenger, MD, for his critical review of this manuscript.

    Abstract

    Objective: To characterize the disposition of total and free serum digoxin following the administration of digoxin Fab antibody in patients with varying degrees of renal function.

    Design: Observational study of pharmacokinetics and pharmacodynamics.

    Setting: Critical care and telemetry units of two university-affiliated teaching institutions, Hartford Hospital and Henry Ford Hospital.

    Patients: Fourteen digoxin-intoxicated patients (baseline total digoxin > 3.2 nmol/mL) with mean (SD) serum creatinine of 380.1 212.2 mol/L who received digoxin Fab antibody therapy.

    Measurements: Serum was drawn every 12 to 24 hours for 80 to 327 hours after Fab administration. Total and free digoxin were assayed in serum by fluorescence polarization immunoassay or modified immunofluorometric assay.

    Results: Before Fab was administered, total digoxin ranged from 3.5 to 10.5 nmol/mL. After treatment with Fab, total digoxin increased rapidly to a mean (SD) maximum of 51.8 22.7 nmol/mL and decreased to 7.2 4.7 nmol/mL at the last measurement. Total digoxin was eliminated in a two-phase fashion. The half-life of the initial phase of total digoxin decline was 11.6 4.1 hours, and the half-life of the second or terminal elimination phase was 118 57 hours. Free digoxin levels decreased rapidly following Fab therapy, to a mean nadir of 0.6 1.1 nmol/mL, but rebounded to a mean maximum free digoxin concentration of 1.7 1.3 nmol/mL in 77 46 hours. The time to maximum free digoxin rebound occurred later in patients with end-stage renal disease (n = 4) compared with other patients (127 40 hours compared with 55 28 hours).

    Conclusion: Elimination of digoxin following Fab therapy is prolonged in digoxin-toxic patients with renal dysfunction. In addition, rebound of free digoxin is delayed in anephric patients. Monitoring free digoxin following the administration of Fab may be of value in selected patients to guide additional Fab dosing, confirm possible rebound toxicity, or guide the reinitiation of digoxin therapy.

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    1. Ann Intern Med August 15, 1993 vol. 119 no. 4 273-277
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