Evaluation of the Effect of Aspirin on  Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies

Annelieke C. Kruithof; Matthijs Moerland; Eleftheria A. Anastasopoulou; Pieter-Jan de Kam; Marieke L. de Kam; Jacobus Burggraaf

doi:10.4236/jbise.2015.81004

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Journal of Biomedical Science and Engine... > Vol.8 No.1, January 2015

Evaluation of the Effect of Aspirin on Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies ()

Annelieke C. Kruithof^1*, Matthijs Moerland^1*, Eleftheria A. Anastasopoulou¹, Pieter-Jan de Kam², Marieke L. de Kam³, Jacobus Burggraaf¹

¹Department of Vascular Medicine, Centre for Human Drug Research, Leiden, The Netherlands.
²Department of Clinical Pharmacology, Merck Sharp & Dohme Corp., Rahway, USA.
³Department of Pharmacometrics, Centre for Human Drug Research, Leiden, The Netherlands.

DOI: 10.4236/jbise.2015.81004 PDF HTML XML 3,321 Downloads 4,334 Views Citations

Abstract

Given the broad application of aspirin as antiplatelet drug, availability of standardized methodology to assess potential interaction with any co-medication on platelet aggregation is desired. We characterized the effect of aspirin (ASA) therapy on collagen-induced platelet aggregation in whole blood to define such methodology. Collagen-induced platelet whole blood aggregation was assessed in 6 healthy male volunteers on 2 occasions (Day 1, Day 7) using the Chronolog aggregometer. From Day 2 up to Day 7, subjects received a daily oral dose of 75 mg ASA. The relationship between collagen dose and platelet aggregation response was assessed. On Day 1, maximal aggregation was observed at 1 μg/mL collagen (15.3 ± 4.6 Ω) and higher. Reproducible results were obtained without any indication of intra-subject fluctuations. ASA treatment decreased maximal aggregation by 80% and 38% at 0.5 and 2.0 μg/mL collagen, respectively. Power calculations were performed based on the observed intra-subject variability and demonstrated minimal sample sizes of 9 - 11 subjects for future cross-over ASA-drug interaction studies exploring effects on platelet aggregation, which demonstrates that the proposed collagen-induced ex vivo whole blood platelet aggregation is a feasible methodology to evaluate ASA-drug interactions in healthy volunteers.

Keywords

Platelet Aggregation, Impedance Aggregometry, Whole Blood, Collagen, Aspirin Interaction

Share and Cite:

Kruithof, A. , Moerland, M. , Anastasopoulou, E. , de Kam, P. , de Kam, M. and Burggraaf, J. (2015) Evaluation of the Effect of Aspirin on Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies. Journal of Biomedical Science and Engineering, 8, 40-45. doi: 10.4236/jbise.2015.81004.

Conflicts of Interest

The authors declare no conflicts of interest.

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