Key result
A single 162 mg or 650 mg dose of chewed and swallowed acetylsalicylic acid achieved >95% inhibition of serum thromboxane B2 within 38 and 22 minutes, respectively, with plasma ASA >686 ng/ml strongly predicting this therapeutic response.
Why the study?
The optimal assessment of therapeutic response and the relationship between pharmacokinetic and pharmacodynamic measurements immediately after an acetylsalicylic acid loading dose remain unclear.
Does a single chewed and swallowed dose of 162 mg or 650 mg acetylsalicylic acid rapidly achieve pharmacokinetic and pharmacodynamic therapeutic thresholds in healthy adults?
RCT (n=10)
Open-label
Randomly assigned
No
Does a single chewed and swallowed dose of 162 mg or 650 mg acetylsalicylic acid rapidly achieve pharmacokinetic and pharmacodynamic therapeutic thresholds in healthy adults?
Immediate pharmacodynamic and pharmacokinetic testing demonstrates strong correlations between acetylsalicylic acid concentration, serum thromboxane B2 inhibition, and arachidonic acid-induced platelet aggregation, establishing potential rapid cutoffs for therapeutic response.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for aspirin response assessment in healthy adults; validation in patients required before clinical consideration.
Despite 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 performed 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)B 2, < 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 TxB 2 (r = 0.74 and p < 0.001), and serum TxB 2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB 2 . 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB 2 , ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB 2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB 2 .
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Gurbel et al. (2023) conducted an RCT in Healthy volunteers (n=10). Acetylsalicylic acid vs. 162 mg vs 650 mg was evaluated on Time to 95% inhibition of serum TxB2 (minutes) (p=NS). A single 162 mg or 650 mg dose of chewed and swallowed acetylsalicylic acid achieved >95% inhibition of serum thromboxane B2 within 38 and 22 minutes, respectively, with plasma ASA >686 ng/ml strongly predicting this therapeutic response.
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