| Abstrakt: |
Aims To investigate the pharmacodynamic interaction of unfractionated heparin (UFH) and acetylic salicylic acid (ASA) on YM337, a monoclonal humanized antibody of the platelet GPIIb/IIIa receptor. Methods In a randomized, placebo-controlled study three treatment groups each with six healthy volunteers received the following medication: group 1, ASA (3 days) + UFH + YM337 (placebo); group 2, ASA (placebo) + UFH (placebo) + YM337; group 3, ASA + UFH + YM337. Assessments were made over 24 h and included bleeding time (BT), ADP (20 µm)- and collagen (5 µg ml-1 )-induced platelet aggregation and PAC1 and CD62 expression measured by flow cytometry. Results In group 3 BT was prolonged to 35 [median, 16–45 min (1,3 quartile)] after UFH administration, increasing to 45 [median, 42–45 min (1,3 quartile)] after YM infusion (6 h). BT remained elevated to 26 [median, 14–45 min (1,3 quartile)] at 24 h, while groups 1 and 2 returned to normal values. Collagen-induced aggregation was 73% [median, 70–80% (1,3 quartile)] under YM337 alone, 79% [median, 72–80% (1,3 quartile)] under ASA + UFH and reduced only in group 3 to 24% [median, 18–29% (1,3 quartile)]. In both groups receiving active YM337, PAC1 expression showed a reduction to < 20% after 6 h of infusion. CD62 expression was not significantly affected by any treatment. Conclusion UFH and YM337 have strong synergistic effects on BT, while coadministration of ASA strongly augments inhibitory effects of YM337 on collagen-induced platelet aggregation. [ABSTRACT FROM AUTHOR] |
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