title: Pharmacodynamic profile of short-term readministration of abciximab in healthy subjects.
abstract: OBJECTIVE
  The purpose of the study was to establish a rebolus regimen for abciximab that restores pharmacologic glycoprotein (GP) IIb/IIIa receptor blockade within a short time frame (up to 48 hours) after completion of an initial treatment.
  
  
  RESULTS
  The study was a single-center, nonrandomized, open-label dose escalation trial in healthy volunteers (n = 30). Each subject received a 0.25 mg/kg bolus and a 0.125 microg/kg per minute infusion of abciximab, followed by incremental bolus doses of the agent at 15-minute intervals up to 48 hours (10 per group) after completion of the infusion, (maximal cumulative rebolus dose of 0.25 mg/kg). Pharmacodynamic measurements (GP IIb/IIIa receptor blockade, turbidimetric and whole blood platelet aggregation with use of a rapid platelet function assay [RPFA]) were obtained at periodic intervals during and after administration of the abciximab bolus and infusion. At the time of the first rebolus, pharmacodynamic measurements were attained immediately before administration of each rebolus and 15 minutes after the last rebolus dose. In subjects who received reboluses 12 hours after infusion, a cumulative dose of 0.05 mg/kg restored >80% blockade of GP IIb/IIIa receptors and >80% inhibition of turbidimetric (5 and 20 micromol/L adenosine diphosphate) and RPFA aggregation in 10 of 10 subjects. At 24 hours after treatment, a cumulative abciximab bolus dose of 0.1 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. At 48 hours after treatment, a cumulative bolus dose of 0.15 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects.
  
  
  CONCLUSIONS
  A fraction of the bolus of abciximab restored pharmacologic (>80%) GP IIb/IIIa receptor blockade when readministered at various postinfusion time points. These observations suggest that in the setting where acute readministration of abciximab is required less than a full bolus dose of the agent is warranted.
authors.affiliation: Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Freedman
authors.forename: Mary A
authors.initials: MA
authors.lastname: Mascelli
authors.forename: John C
authors.initials: JC
authors.lastname: Pezzullo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: Bart
authors.initials: B
authors.lastname: Frederick
authors.forename: Robert E
authors.initials: RE
authors.lastname: Jordan
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Abernethy
mesh_terms: D000077284:Abciximab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab