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


CONCLUSIONS
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.
Tsuruoka
S
S
Department of Clinical Pharmacology, Jichi Medical School, Kawachi, Tochigi, Japan. tsuru@jichi.ac.jp
Osono
E
E
Nishiki
K
K
Kawaguchi
A
A
Arai
T
T
Furuyoshi
S
S
Saito
T
T
Takata
S
S
Sugimoto
K
K
Kurihara
S
S
Fujimura
A
A
D000327:Adsorption; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001772:Blood Cell Count; D002316:Cardiotonic Agents / Q000302:isolation & purification* / Q000506:poisoning*; D004077:Digoxin / Q000302:isolation & purification* / Q000506:poisoning*; D004285:Dogs; D005260:Female; D006464:Hemoperfusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
D000418:Albumins; D002316:Cardiotonic Agents; D001613:beta 2-Microglobulin; D004077:Digoxin