Occupancy of the internal and external pools of glycoprotein IIb/IIIa following abciximab bolus and infusion

The internal pool of GPIIb/IIIa, which is expressed upon platelet activatio n, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determin e the occupancy of the internal and external pools of GPIIb/IIIa and platel et function following an abciximab bolus and infusion, 15 patients undergoi ng elective percutaneous transluminal coronary angioplasty were administere d abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and oc cupancy in resting and TRAP-6 (20 muM) activated samples (to expose the int ernal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhib ition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupan cy (range 82-99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 muM AD P (maximal, 11 +/- 2% of baseline), but less so to 5 muM TRAP-6 (maximal, 3 6 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappe arance of abciximab from the platelet surface. Maximum inhibition of platel et function and receptor occupancy of the external pool of GPIIb/IIIa occur s within 3 min of an abciximab bolus and infusion. However, some internal r eceptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.