Irreversibly acetylates arachidonic acid cascade COX-1 (platelets, GI mucosa) + COX-2 (inflammation). At low dose (81 mg), COX-1 inhibition dominates → platelet aggregation TxA2 suppression → antiplatelet for 7–10 d (RBC lifetime). At higher dose, COX-2 contributes → analgesia, anti-inflammation. Unique vs other NSAIDs in being the only one that irreversibly inhibits platelet function.
Half-Life (t½)
PO: 0.3h
Dosing Guidelines
PO: Typical 433 mg (Range: 325–650 mg)
Target Organ Systems
immune-hematologic
Interactions
Ibuprofen (caution): Ibuprofen may block aspirin's COX-1 acetylation site if taken within 2 h prior — reduces cardioprotective effect.
Valproate (major): Canonical clinical displacement. Goulden 1987 (PMID:6804150) n=6 epileptic children on VPA + aspirin: "the steady-state serum free fractions of VPA rose from 12% to 43%" — Δfu = (0.43 − 0.12)/0.12 ≈ 2.58. Free-VPA spike >3× drives toxicity; high-dose aspirin combination should be avoided in epilepsy patients on chronic VPA.
Pathways It Modulates
AMPK energy sensor (activator) — AMPK (salicylate direct β1-subunit binding; Hawley 2012)