| Autor: |
Klinkhardt, Ute, Graff, Jochen, Westrup, Dagmar, Kirchmaier, Carl M., Esslinger, Hans-Ulrich, Breddin, Hans Klaus, Harder, Sebastian |
| Předmět: |
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| Zdroj: |
British Journal of Clinical Pharmacology; Sep2001, Vol. 52 Issue 3, p297-305, 9p |
| Abstrakt: |
Aims The objective of our study was to define the interaction between either unfractionated heparin (UFH) or a low molecular weight heparin, reviparin (REV), and the pharmacodynamic profile of the GPIIb/IIIa-antagonists abciximab (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 received UFH (5000 IU bolus/infusion 7 IU kg-1 h-1 for 7 h, n = 6), REV (4200-anti-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 effects measured were bleeding time (BT), fibrinogen-binding at the GPIIb/IIIa-receptor (FIB), expression of the platelet secretion marker CD62, and ADP (20 µm)- and collagen (5 µg ml-1)-induced platelet aggregation. Results After treatment with both GPIIb/IIIa-antagonists, prolongation of BT occurred to a similar magnitude (approximately 25–30 min) and was not affected by UFH or REV-comedication. ABC or T with ASA alone resulted in nearly the same magnitude of reduction in FIB and platelet aggregation. After coadministration 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. Inhibition 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 changes were noted with REV. Minor reductions in CD62-expression were seen in subjects given ABC or T alone, but expression was not affected by UFH or REV. Conclusions Co-medication with UFH attenuated platelet inhibition during treatment with GPIIb/IIIa-antagonists, but these effects were not seen with the low molecular weight... [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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