Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade

Article

关键词: GLYCOPROTEIN IIB-IIIA;    CHIMERIC 7E3 FAB;    MONOCLONAL-ANTIBODIES;    CORONARY ANGIOPLASTY;    C7E3 FAB;    AGGREGATION;    ACTIVATION;    COMPLEX;    BINDING;    FRAGMENT;   

DOI  :  10.1161/01.CIR.97.17.1680

来源: SCIE

【 摘 要 】

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 mu g/min (EPIC regimen) or 0.125 mu g . 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.

【 授权许可】

Free