The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin.
We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) (respectively, TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha)) to determine the optimal dosage and formulation of aspirin to inhibit TXA2 production while sparing PGI2. In a randomized, parallel study, 52 healthy male volunteers (62 independent observations) with no history of bleeding disorders were given 80 mg or 325 mg of regular aspirin, or 325 mg of enteric-coated aspirin to ingest daily (14 pills) or every other day (7 pills) for a continuous 14 day period. Bleeding times were performed on day 1 before aspirin, 6 h after aspirin on day 1, and before aspirin on day 14. Bleeding times, plasma volume, and total volume increased significantly from before aspirin to after 6 h and 14 days (p < 0.0001 for all parameters) for all aspirin formulations. For day 1 before aspirin ingestion to 6 h later, both TX and PGI2 (p < 0.008) decreased significantly. 6 h after ingestion of aspirin on day 1 to day 14, both TX and PGI2 levels also significantly decreased (p < 0.0001). There was a highly significant decrease in PGI2 production on every other day aspirin schedules (p = 0.0001) particularly with 80 mg of aspirin, while the decrease in PGI2 production on daily aspirin was not significant (p = 0.10). The most favourable ratio of 6-keto-PGF1 alpha to TXB2 occurred with 80 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)
Gow
J A
JA
Manitoba Institute of Cell Biology, Faculty of Medicine, University of Manitoba, Winnipeg.
Ebbeling
L
L
Gerrard
J M
JM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001760:Bleeding Time; D004304:Dosage Forms; D015777:Eicosanoids / Q000097:blood*; D011464:Epoprostenol / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D004304:Dosage Forms; D015777:Eicosanoids; D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001241:Aspirin