Inter-individual variations of the effect of low dose aspirin regime on platelet cyclooxygenase activity.
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 microgram aspirin administered per kg bw, a positive correlation was established to the activity before medication. It was found that doses exceeding 1500 micrograms 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.
Department of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden.
H
H
Beving
S
S
Eksborg
R S
RS
Malmgren
R
R
Nordlander
L
L
Rydén
P
P
Olsson
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D012016:Reference Values; D012459:Salicylates / Q000097:blood; D020156:Salicylic Acid
D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D012459:Salicylates; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D020156:Salicylic Acid; D001241:Aspirin