From Centocor, Malvern, Pa.
Correspondence to Marian T. Nakada, PhD, Centocor, 200 Great Valley Pkwy, Malvern, PA 19355. E-mail nakadam{at}centocor.com
Background—Large, randomized, and
blinded clinical trials (EPIC, EPILOG, and CAPTURE) have demonstrated
that abciximab (ReoPro, chimeric 7E3 Fab) markedly reduces thrombotic
events associated with percutaneous transluminal
coronary interventions. The marked early benefits at 30 days
were sustained at 6 months and 3 years. Initially developed because of
its efficacy in blocking GP IIb/IIIa
(
Methods and Results—This study presents a detailed
characterization of the
Conclusions—As an antagonist of not only GP IIb/IIIa
but also
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Abciximab (ReoPro, Chimeric 7E3 Fab) Demonstrates Equivalent Affinity and Functional Blockade of Glycoprotein IIb/IIIa and
vß3 Integrins
IIb/ß3) receptors on platelets,
abciximab also binds with equivalent affinity to
vß3. vß3 interaction,
including the ability of abciximab to (1) bind with comparable affinity
to vß3 and GP IIb/IIIa, (2) inhibit
vß3 and GP IIb/IIIa–mediated cell
adhesion in vitro with IC50 values approximating binding
KD values, and (3) redistribute between GP
IIb/IIIa and vß3 integrins in
vitro. vß3, abciximab may provide
additional clinical benefit in preventing
vß3-mediated effects such as thrombin
generation, clot retraction, or smooth muscle cell migration and
proliferation. Abciximab binds with equivalent affinity to both GP
IIb/IIIa and vß3 and redistributes between
the 2 integrin receptors in vitro. Abciximab has been previously shown
to circulate on platelets for up to 2 weeks. Taken together, these
findings suggest that abciximab may have the ability to inhibit both GP
IIb/IIIa and vß3 for extended periods.
Key Words: glycoproteins • antibodies • platelet aggregation inhibitors
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