Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response

AbstractDespite decades of investigations, the optimal assessment of the “therapeutic response” to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were perf ormed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as >  95% inhibition of serum thromboxane (Tx)B2, <  550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p <  0.001), serum TxB2 (r  = 0.74 and p <  0.001), and serum TxB2 inhibition (r  = 0.79, p <  0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with >  95% inhibition of TxB2. 686  ng/ml plasma ASA cut-off point was associated with >  95% inhibition of serum TxB2,  ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked i...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research