Aspirin kinetics and platelet aggregation in man.

Area of Science:

• Pharmacology
• Biochemistry
• Cardiovascular Medicine

Background:

• Aspirin (ASA) is widely used for its antiplatelet effects.
• Different ASA formulations exist, varying in release profiles and excipients.
• Understanding the relationship between ASA pharmacokinetics and pharmacodynamics is crucial for optimizing antiplatelet therapy.

Purpose of the Study:

• To evaluate the in vitro effects of six commercial aspirin preparations on platelet aggregation.
• To correlate changes in platelet function with aspirin pharmacokinetics.
• To investigate potential differences in the onset and duration of antiplatelet effects among various ASA formulations.

Main Methods:

• Six healthy subjects received single oral doses of six different aspirin preparations in a randomized crossover design.
• Blood samples were collected at various time points post-dosage for analysis of plasma aspirin and salicylic acid levels.
• In vitro platelet aggregation was measured in response to collagen and adenosine diphosphate stimulation.

Main Results:

• All tested aspirin preparations demonstrated comparable inhibition of platelet aggregation.
• Rapid-release formulations showed peak plasma aspirin levels within 60 minutes and salicylic acid levels within 2 hours.
• Delayed-release formulations (Ecotrin, S.R.A.) showed no measurable aspirin but significant salicylic acid levels, with platelet inhibition occurring without detectable circulating aspirin.

Conclusions:

• Commercial aspirin preparations exhibit similar antiplatelet efficacy.
• Delayed-release formulations may achieve platelet inhibition through mechanisms independent of circulating aspirin, potentially involving portal circulation acetylation.
• Further research is warranted to elucidate the specific mechanisms of delayed-release aspirin and their clinical implications.