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From the Department of Clinical Pharmacology, Centocor Inc, Malvern, Pa.
Background—The
glycoprotein (GP) IIb/IIIa receptor antagonist
abciximab is approved for use in high-risk percutaneous
coronary interventions. The purpose of the present study
was to establish the pharmacodynamic profile and platelet-bound
life span of abciximab.
Methods and Results—The pharmacodynamics of abciximab (inhibition
of ex vivo platelet aggregation and GP IIb/IIIa receptor blockade)
were measured in 41 individuals who were randomized to receive a
0.25-mg/kg bolus and a 12-hour infusion of either 10 µg/min (EPIC
regimen) or 0.125 µg · kg-1 ·
min-1 (EPILOG regimen) of the antiplatelet agent. At
extended times, the amount and distribution of platelet-bound
abciximab were monitored by flow cytometry. The EPIC and EPILOG
infusion regimens exhibited equivalent blockade of both GP IIb/IIIa
receptors and platelet aggregation throughout the duration of
abciximab treatment. Flow cytometry revealed a single, highly
fluorescent platelet population during treatment,
consistent with complete saturation and homogeneous
distribution of abciximab on circulating platelets. For 15 days
after treatment, the fluorescence histograms remained unimodal
with gradually diminishing fluorescence intensity, indicating
decreasing levels of platelet-bound abciximab. At 8 and 15 days,
which exceeds the normal circulating life span of platelets, median
relative fluorescence intensity corresponded to 29 100 (29%
GP IIb/IIIa receptor blockade) and 13 300 (13% GP IIb/IIIa receptor
blockade) abciximab molecules bound per platelet, respectively.
Conclusions—These results are consistent with continuous
reequilibration of abciximab among circulating platelets and may
explain the gradual recovery of platelet function and long-term
prevention of ischemic complications by abciximab after
coronary intervention.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Pharmacodynamic Profile of Short-term Abciximab Treatment Demonstrates Prolonged Platelet Inhibition With Gradual Recovery From GP IIb/IIIa Receptor Blockade
Key Words: drugs • pharmacology • receptors
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