Figure 5.

Models of variable responsiveness to low-dose aspirin given once daily. The figure depicts models of pharmacodynamic- (PD-) or pharmacokinetic- (PK-) related variable pharmacological response to aspirin, as measured by serum TXB₂. Under normal conditions (left panel) aspirin inhibits peripheral platelets and bone-marrow megakaryocytes (MKs) resulting in a relatively steady inhibition of platelet COX activity over the 24 hour dosing interval. In case of increased platelet turnover (mid panel), the short-lived aspirin appears unable to acetylated new platelets which are released from MKs during the 24 hour dosing interval, thus resulting in a progressive increase in TXA₂ generation between 12 and 24 hours after dosing. In case of variation in drug's PK (right panel), a reduced drug bioavailability in the portal and/or in the systemic circulation would lead to a suboptimal platelet TXA₂ generation already at early time points (6–12 hours) after drug intake. Unacetylated platelets are represented in green. EC: enteric coated.