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.
RCT (n=10)
Open-label
Randomly assigned
No
What is the relationship between pharmacokinetic and pharmacodynamic parameters immediately following an oral loading dose of acetylsalicylic acid in healthy adults?
Pharmacodynamic and pharmacokinetic parameters correlate closely immediately following an oral ASA loading dose, with therapeutic response achieved within 30 minutes.
Absolute Event Rate: 38% vs 22%
p-value: p=NS
Abstract 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, 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 .
Gurbel et al. (Fri,) conducted a 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.