Effects of PEG-Hirudin in Clotting Parameters and Platelet Function and its Interaction with Aspirin in Healthy Volunteers
| Autor: | Piotr Radziwon, Hans Klaus Breddin, Hans-Ulrich Esslinger, Stephan Köhne, Jeanine M. Walenga |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Blood Platelets
0301 basic medicine Bleeding Time Activated clotting time 030204 cardiovascular system & hematology Placebo 03 medical and health sciences 0302 clinical medicine Bolus (medicine) Reference Values Bleeding time medicine Humans Blood Coagulation Aspirin Cross-Over Studies medicine.diagnostic_test business.industry Hematology General Medicine Hirudins 030104 developmental biology Pharmacodynamics Anesthesia Ecarin clotting time business Platelet Aggregation Inhibitors Partial thromboplastin time medicine.drug |
| Zdroj: | Clinical and Applied Thrombosis/Hemostasis. 9:79-88 |
| ISSN: | 1938-2723 1076-0296 |
| DOI: | 10.1177/107602960300900111 |
| Popis: | The purpose of this study was to investigate the pharmacodynamics of PEG-Hirudin and its potential interactions with acetylsalicylic acid (ASA 325 mg once daily from days 1-3). In a randomized, 2-way cross-over trial, 6 healthy volunteers received PEG-Hirudin (IV bolus of 0.2 mg/kg + 0.02 mg/kg/h for 24 hours) and placebo (IV bolus + 24-hour infusion). In a further randomized, 3way cross-over trial another 9 healthy volunteers received ASA (325 mg) or oral placebo from days 1 to 3 and PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 h) or IV placebo on day 3. Assessments included bleeding time (BT), collagen (1 μg ml-1)-induced platelet aggregation (CIPA), platelet adhesion, ecarin clotting time (ECT), activated clotting time (ACT), plasma anti-factor Ila activity (aIla), and activated partial thromboplastin time (aPTT). Ten minutes after the PEG-Hirudin injection/starting the infusion, mean plasma concentration was 3.1 μg/mL and aPTT, ECT, and ACT were prolonged up to 80, 309, and 233 seconds, respectively. During the last 8 hours of the 24-hour infusion mean PEG-Hirudin plasma concentration was 1.3 μg/mL. In the interaction study, ASA significantly inhibited CIPA. At 6 hours after administration, on day 3 mean BT was 6.5 minutes after PEG-Hirudin alone, 18.2 minutes after ASA alone, and 32.9 minutes after combined administration of ASA and PEG-Hirudin. PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 hours) administered alone or together with 325 mg ASA proved to be safe in healthy volunteers. Combined use of PEG-Hirudin and ASA significantly increased the mean bleeding time compared to ASA or PEG-Hirudin monodrug administration. None of the clotting parameters or platelet function tests correlated with the prolongation of the bleeding time. |
| Databáze: | OpenAIRE |
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