Relationship of Arachidonic Acid Concentration to Cyclooxygenase-Dependent Human Platelet Aggregation

Inhibition of ex vivo arachidonic acid (AA)–induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX‐1 but not COX‐2. At low concentrations, there is broad inter‐ and intrasubject variability in AA‐induced aggregation of platelets...

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Published in:Journal of clinical pharmacology 2003-09, Vol.43 (9), p.983-989
Main Authors: Burke, Joanne, Kraft, Walter K., Greenberg, Howard E., Gleave, Melanie, Pitari, Giovanni M., VanBuren, Sandi, Wagner, John A., Waldman, Scott A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Arachidonic acid
Arachidonic Acid - blood
Arachidonic Acid - pharmacology
Aspirin - administration & dosage
Aspirin - pharmacology
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
cyclooxygenase inhibitors
Cyclooxygenase Inhibitors - administration & dosage
Cyclooxygenase Inhibitors - pharmacology
Drug Administration Schedule
Drug Interactions
Female
Humans
low-dose aspirin therapy
Male
Medical sciences
Middle Aged
pharmacodynamics
pharmacokinetics
Pharmacology. Drug treatments
platelet aggregation
Platelet Aggregation - drug effects
Prostaglandin-Endoperoxide Synthases - blood
Reproducibility of Results
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Summary:Inhibition of ex vivo arachidonic acid (AA)–induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX‐1 but not COX‐2. At low concentrations, there is broad inter‐ and intrasubject variability in AA‐induced aggregation of platelets ex vivo. This study defined a concentration that reliably induces aggregation without overcoming inhibition by therapeutic aspirin therapy (ASA, 81‐mg) treatment. Logistic regression analysis of ex vivo aggregation, induced with increasing concentrations of AA in platelet‐rich plasma (PRP), estimated that platelets from ≥ 90% of subjects would aggregate at ≥ 1.5 mM AA (95% confidence interval [CI], 1.1, 2.1). A concentration of 1.6 mM AA failed to aggregate platelets from 26 healthy volunteers, who had previously aggregated at this concentration, following six daily oral doses of 81 mg of ASA. These data demonstrate that 1.6 mM AA reproducibly induces platelet aggregation in PRP from healthy volunteers without overcoming the antiplatelet effect of daily low‐dose aspirin therapy.
ISSN:0091-2700
1552-4604
DOI:10.1177/0091270003257216