Evaluation of the Effect of Aspirin on Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies
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Author(s)
Annelieke C. Kruithof1*, Matthijs Moerland1*, 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.
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.
Cite this paper
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