Inter-individual variations of the effect of low dose aspirin regime on platelet cyclooxygenase activity

• Published in: Thrombosis research Vol. 74; no. 1; pp. 39 - 51
• Main Authors: Beving, Håkan, Eksborg, Staffan, Malmgren, Rigmor Stain, Nordlander, Rolf, Rydén, Lars, Olsson, Per
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01.04.1994; Elsevier Science
• Subjects: 12-HHT; Adult; Aspirin - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - enzymology; Blood. Blood coagulation. Reticuloendothelial system; cyclooxygenase activity; Cyclooxygenase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated - blood; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; platelets, low dose aspirin; Prostaglandin-Endoperoxide Synthases - blood; Reference Values; Salicylates - blood; Salicylic Acid; cyclooxygenase activity; 12-HHT; platelets, low dose aspirin; Non steroidal antiinflammatory agent; Human; Prostaglandin-endoperoxide synthase; Platelet; Enzymatic activity; Enzyme; Low dose; Interindividual comparison; Oxidoreductases; Salicylates; Antiplatelet agent
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(94)90034-5

Thirteen healthy men (age range 24–59 years) received three single doses (30, 75, and 150 mg/day) of aspirin for seven days, followed by a wash-out period of three weeks, in a randomized order. The arachidonic acid metabolite 12-L-5,8,10-heptadecatrienoic acid (12-HHT) was taken as a measure of platelet cyclooxygenase activity. There was a large inter-individual variation in 12-HHT production prior to and during aspirin treatment. After one week of treatment the mean reduction was 69, 72 and 83 % for the doses 30, 75 and 150 mg/day respectively. When the degree of cyclooxygenase inhibition was expressed per μg aspirin administered per kg bw, a positive correlation was established to the activity before medication. It was found that doses exceeding 1500 μg per kg bw is required to achieve a predictable reduction in cyclooxygenase activity. Thus, by determining the pre-treatment cyclooxygenase activity in an individual it should be possible to adjust the enzyme activity to any desired level below 40 % of its initial value. 150 mg aspirin/day for one week had a stimulating effect on the platelet basal production of 12-HHT when measured three weeks after the cessation of treatment. This rebound phenomenon was also observed up to six weeks after a single dose of 600 or 1200 mg of aspirin.