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Relationship of Arachidonic Acid Concentration to Cyclooxygenase‐Dependent Human Platelet Aggregation
Author(s) -
Burke Joanne,
Kraft Walter K.,
Greenberg Howard E.,
Gleave Melanie,
Pitari Giovanni M.,
VanBuren Sandi,
Wagner John A.,
Waldman Scott A.
Publication year - 2003
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270003257216
Subject(s) - ex vivo , platelet , arachidonic acid , aspirin , cyclooxygenase , in vivo , pharmacology , chemistry , medicine , biochemistry , in vitro , enzyme , biology , microbiology and biotechnology
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.