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

Citation
S. Tsuruoka et al., Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: A potential use for digoxin intoxication, CLIN PHARM, 69(6), 2001, pp. 422-430
Citations number
36
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
00099236 → ACNP
Volume
69
Issue
6
Year of publication
2001
Pages
422 - 430
Database
ISI
SICI code
0009-9236(200106)69:6<422:RODBCF>2.0.ZU;2-K
Abstract
Background: A beta (2)-microglobulin adsorption column used for the treatme nt 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 colum n was measured by a single use of the column in 8 patients receiving hemodi alysis with a therapeutic level of digoxin. In vitro adsorption was evaluat ed by use of incubation with adsorbent of the column and digoxin or ranitid ine, a hydrophilic drug. Clearance with the beta (2)-microglobulin column w as 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 c olumn in the patients. Digoxin clearance with the beta (2)-microglobulin co lumn was about 145 +/- 20 ml/min, with a blood flow rate of 160 to 220 ml/m in (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed i n vitro, and the capacity of the beta (2)-microglobulin column was not satu rated until a toxic level was reached (50 ng/mL). This value was higher tha n that obtained with use of charcoal. In dogs with digoxin intoxication, di goxin clearance was 38.9 +/- 1.5 ml/min, with a blood flow rate of 50 ml/mi n (95% of plasma flow rate), which was almost twice as that achieved with c harcoal. The degree of thrombocytopenia and leukopenia was small with use o f the beta (2)-microglobulin column. Conclusion: These data suggested that the beta (2)-microglobulin column sel ectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.