Removal of Digoxin from the Circulation Using Immobilized Monoclonal Antibodies

Brizgys, Marius V.; Pincus, Seth H.; Siebert, Christopher J.; Rollins, Douglas E.

doi:10.1002/jps.2600780510

Cited by 5 publications

(1 citation statement)

References 19 publications

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“…Monoclonal antibodies against digoxin have been used in the therapeutic reversal of digoxin intoxication (7,8,9), pharmacokinetic studies (10) and the development of digoxin immunoassays (11). Such assays, however, show low specificity because of interference by structural analogs and mainly by digoxin metabolites (12).…”

Section: Introductionmentioning

confidence: 99%

Novel Anti-Digoxin Monoclonal Antibodies with Different Binding Specificities for Digoxin Metabolites and Other Glycosides

Wahyono

Piechaczyk²,

Mourton³

et al. 1990

Hybridoma

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Spleen cells of BALB/c mice immunized with a digoxin-bovine serum albumin conjugate were fused with P3-X63-Ag8.653 mouse myeloma cells. Seven monoclonal antibodies (MAb) selected by indirect ELISA were produced, purified and characterized. All the MAb were IgG1 isotypes. The apparent equilibrium association constants (Ka) of four of the MAb, determined by Scatchard analysis of the RIA data, ranged from 1 x 10(9) M-1 to 5.9 x 10(9) M-1. The estimated Ka values of the three other MAb were found to be between 4.8 x 10(7) M-1 and 5.9 x 10(8) M-1. Using digoxin and eighteen structurally-related compounds, the seven MAb could be divided into five groups based on their binding specificities assessed by an inhibition immunoenzymatic test. The MAb in Groups I and II, in particular, showed very different specificity profiles: the two MAb in Group I had low cross-reactivity with cardioinactive digoxin metabolites, whereas the high affinity MAb in Group II recognized all the digoxin metabolites tested. The MAb in Group I might be useful in a digoxin immunoassay and the Group II MAb in therapeutic reversal of digoxin intoxication.

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Section: Introductionmentioning

confidence: 99%