M. Buerke et al., ASPIRIN THERAPY - OPTIMIZED PLATELET INHIBITION WITH DIFFERENT LOADING AND MAINTENANCE DOSES, The American heart journal, 130(3), 1995, pp. 465-472
Inhibition of cyclooxygenase by aspirin has been shown to be beneficia
l in clinical situations such as acute myocardial infarction or unstab
le angina. The precise effect of various doses of aspirin on acute and
long-term inhibition of platelet aggregation and thromboxane synthesi
s remains unclear. In this study we evaluated the effect of oral aspir
in (0, 40, 100, 300, or 500 mg) as the initial loading dose in combina
tion with different maintenance doses of aspirin (0, 40, or 100 mg/day
) for 14 days on platelet function in healthy men. Bleeding time 2 or
24 hours after the first aspirin administration was significantly incr
eased for 300 and 500 mg aspirin (p < 0.01). Two hours after the first
administration of 100, 300, and 500 mg aspirin, a significant inhibit
ion of collagen-induced platelet aggregation (ED(50) collagen: from 3
+/- 1 to 17 +/- 2, 24 +/- 3, 22 +/- 3 mu g/ml, respectively) was seen.
At the same time serum thromboxane B-2 synthesis was inhibited by mor
e than 99% with 300 and 500 mg aspirin. At the end of the 14-day obser
vation period, bleeding time was significantly prolonged for the diffe
rent combinations of aspirin doses compared with initial values (p < 0
.01). Collagen-induced platelet aggregation and serum thromboxane B-2
synthesis were significantly inhibited for all aspirin combinations te
sted at 14 days (p < 0.05). The 40/40 mg aspirin combination was less
effective, because it reached its maximal effect very late at day 7 of
the observation period compared with the other combinations. The resu
lts of our study indicate that a loading dose of 300 mg aspirin in com
bination with 40 mg as a maintenance dose resulted in sufficient inhib
ition of platelet aggregation and of thromboxane synthesis during the
14-day observation period.