Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: a potential use for digoxin intoxication

Clin Pharmacol Ther. 2001 Jun;69(6):422-30. doi: 10.1067/mcp.2001.116061.

Abstract

Background: A beta(2)-microglobulin adsorption column used for the treatment of dialysis-related amyloidosis removes serum beta(2)-microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin.

Methods: In vivo clearance of digoxin with the beta(2)-microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the beta(2)-microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin.

Results: Digoxin concentration was reduced from 1.11 +/- 0.25 ng/mL to 0.57 +/- 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the beta(2)-microglobulin column was about 145 +/- 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed in vitro, and the capacity of the beta(2)-microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 +/- 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the beta(2)-microglobulin column.

Conclusion: These data suggested that the beta(2)-microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Albumins / metabolism
  • Animals
  • Blood Cell Count
  • Cardiotonic Agents / isolation & purification*
  • Cardiotonic Agents / poisoning*
  • Digoxin / isolation & purification*
  • Digoxin / poisoning*
  • Dogs
  • Female
  • Hemoperfusion
  • Humans
  • Male
  • Middle Aged
  • Renal Dialysis
  • beta 2-Microglobulin / chemistry*
  • beta 2-Microglobulin / metabolism

Substances

  • Albumins
  • Cardiotonic Agents
  • beta 2-Microglobulin
  • Digoxin