Effects on cyclo-oxygenase of low and high dose aspirin.
The study was undertaken to develop clinically applicable methods to detect the influence of low dose treatment with acetylsalicylic acid (ASA) on the platelet function. The cyclooxygenase activity of the platelets was measured by determination of the metabolite 12-HHT after challenge with arachidonic acid. Two healthy subjects received 600 mg ASA in a single dose. Two hours after intake the salicylate concentration level in plasma was 600 nmol/ml, with a 90 per cent reduction after 24 hours. The platelet cyclooxygenase activity (12-HHT) was completely and irreversibly inhibited within two hours after ASA intake. Five subjects received 75 mg ASA for eight consecutive days. The salicylate concentrations two hours after the intake of the first and last tablet were within 65 and 71 nmol/ml plasma, indicating that no accumulation of salicylate occurred during the treatment period. The decrease in cyclooxygenase activity during low dose treatment varied in the different subjects between 60 and 90 per cent. The rate of recovery of cyclooxygenase activity after termination of the low dose ASA treatment was faster than after the large single dose.
Beving
H
H
Department of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden.
Eksborg
S
S
Nordlander
R
R
Olsson
P
P
Olsson
U
U
D000328:Adult; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006403:Hematologic Tests; D006801:Humans; D008297:Male; D008875:Middle Aged
D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D001241:Aspirin