Pharmacodynamic characterization of the interaction between abciximab or tirofiban with unfractionated or a low molecular weight heparin in healthy subjects

Aims The objective of our study was to define the interaction between eithe r unfractionated heparin (UFH) or a low molecular weight heparin, reviparin (REV), and the pharmacodynamic profile of the GPIIb/IIIa-antagonists abcix imab (ABC) or tirofiban (T). Methods Two studies each containing 18 healthy subjects were performed, and all were pretreated with aspirin (ASA) for 3 days. Volunteers then receive d UFH (5000 IU bolus/infusion 7 IU kg(-1) h(-1) for 7 h, n=6), REV (4200-an ti-Xa-IU s.c., n = 6) or placebo (n = 6). One hour later, ABC (study I) or T (study II) were given by i.v. infusion for 6 h. The pharmacodynamic effec ts measured were bleeding time (BT), fibrinogen-binding at the GPIIb/IIIa-r eceptor (FIB), expression of the platelet secretion marker CD62, and ADP (2 0 mum)- and collagen (5 mug ml(-1))-induced platelet aggregation. Results After treatment with both GPIIb/IIIa-antagonists, prolongation of B T occurred to a similar magnitude (approximately 25-30 min) and was not aff ected by UFH or REV-comedication. ABC or T with ASA alone resulted in nearl y the same magnitude of reduction in FIB and platelet aggregation. After co administration with UFH, FIB was significantly higher (thus less inhibited) than after after T+ASA alone (19 +/- 16% vs 55 +/- 36%) or ABC+ASA alone ( 8 +/- 9% vs 32 +/- 11%). This attenuation of FIB was not seen with REV. Inh ibition of ADP-and collagen-induced aggregation tended to be attenuated by treatment with UFH (e.g. ADP-induced aggregation at 0.25 h after ABC + ASA alone = 13 +/- 4%; after coadministration with UFH = 40 +/- 26%). No such c hanges were noted with REV. Minor reductions in CD62-expression were seen i n subjects given ABC or T alone, but expression was not affected by UFH or REV. Conclusions Co-medication with UFH attenuated platelet inhibition during tr eatment with GPIIb/IIIa-antagonists, but these effects were not seen with t he low molecular weight heparin reviparin. The results show that administra tion of reviparin together with abciximab or tirofiban did not adversely af fect the pharmacodynamic profile of these GPIIb/IIIa-antagonists.