Figure 3.

Aspirin antiplatelet pharmacodynamics in healthy subjects. (A) Tridimensional model of human PGG/H synthase-1. Acetylation of Ser-529 by aspirin permanently blocks the COX-1 channel near the catalytic pocket. (B) Inhibition of platelet thromboxane A₂ production by oral aspirin in healthy subjects. Thromboxane A₂ production during whole blood clotting was measured before and 24 h after a single aspirin ingestion. The results are expressed as per cent inhibition, each subject serving as his or her own control. Mean values ± 1 SD are plotted. Numbers in parentheses indicate the number of subjects for each dose of aspirin. Reproduced from Patrignani et al., J Clin Invest 1982, with permission from the American Society for Clinical Investigation. (C) Long-term effects of low-dose (0.45 mg/kg per day) aspirin on platelet thromboxane A₂ and renal PGI₂ synthesis. Serum thromboxane A₂ concentrations and urinary excretion of 6-keto-PGF_Iα were measured in three healthy subjects before, during, and after aspirin therapy. Mean values ± SEM are plotted. Reproduced from Patrignani et al., J Clin Invest 1982, with permission from the American Society for Clinical Investigation. (D) Dose dependence of the inhibition of platelet thromboxane B₂ production by aspirin. Serum thromboxane B₂ was measured before and after single (▴) or daily (●) dosing with aspirin in four healthy subjects. Individual data are expressed as per cent inhibition, with each subject serving as his or her own control. Daily dosing values represent measurements obtained at steady-state inhibition. ID₅₀ = 50% inhibitory dose. Reproduced from Patrono et al.,¹⁰ with permission from Wolters Kluwer Health, Inc. SD, standard deviation; ID₅₀, 50% inhibitory dose; TXB₂, thromboxane B₂