Relationship of arachidonic acid concentration to cyclooxygenase-dependent human platelet aggregation.
Publication/Presentation Date
9-1-2003
Abstract
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 > or = 90% of subjects would aggregate at > or = 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.
Volume
43
Issue
9
First Page
983
Last Page
989
ISSN
0091-2700
Published In/Presented At
Burke, J., Kraft, W. K., Greenberg, H. E., Gleave, M., Pitari, G. M., VanBuren, S., Wagner, J. A., & Waldman, S. A. (2003). Relationship of arachidonic acid concentration to cyclooxygenase-dependent human platelet aggregation. Journal of clinical pharmacology, 43(9), 983–989. https://doi.org/10.1177/0091270003257216
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
12971030
Department(s)
Administration and Leadership
Document Type
Article