title: Comparison of the pharmacokinetics and in vivo bioaffinity of DigiTAb versus Digibind.
abstract: The in vivo digoxin binding affinity and normal pharmacokinetic values of digoxin-immune Fab are unknown. Healthy subjects (n = 16) were randomized to one of the two digoxin-immune Fab products, DigiTAb or Digibind, to compare the in vivo digoxin binding affinity and pharmacokinetic disposition. Each subject received 1 mg of intravenous digoxin infused during 5 minutes followed 2 hours later by 76 mg of either DigiTAb or Digibind. Both Fab products reduced free digoxin serum concentrations to below assay detection with equal ability. Consequently, total digoxin serum concentrations increased approximately 10-fold. Peak total digoxin serum concentrations post-Fab dosing were similar to the pre-Fab peak digoxin concentration for both Fab products (45 +/- 14 and 44 +/- 11 for DigiTAb, pre and post, respectively) 50 +/- 17 and 41 +/- 9 for Digibind, pre and post, respectively) indicating in vivo equimolar binding affinity. While bioaffinity for digoxin was equal between groups, total digoxin area under the curve (AUC) and digoxin-immune Fab AUC were lower in the DigiTAb group compared with the Digibind group. Hence, systemic total digoxin and Fab clearance were greater in the DigiTAb-treated group. In conclusion, equimolar doses of both DigiTAb and Digibind completely bind digoxin in vivo. The ability of digoxinimmune Fab to bind to digoxin is not affected by the systemic disposition of the Fab product.
authors.affiliation: Protherics Inc., Augusta, Georgia, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Ward
authors.forename: L
authors.initials: L
authors.lastname: Sjostrom
authors.forename: M R
authors.initials: MR
authors.lastname: Ujhelyi
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004077:Digoxin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007262:Infusions, Intravenous; D008297:Male; D012016:Reference Values
chemical_list: D000889:Anti-Arrhythmia Agents; D007140:Immunoglobulin Fab Fragments; D004077:Digoxin