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

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DOI: 10.4236/jbise.2015.81004 2,946 Downloads 4,141 Views

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

Affiliation(s)

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.

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

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

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.

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