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Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.Rapidly metabolized to salicylic acid; plasma aspirin concentrations are undetectable 1–2 hours after administration. Peak plasma salicylic acid concentrations attained within 1–2 hours following administration of uncoated tablets.

Slowly and variably absorbed following rectal administration.

Onset

Single oral doses of rapidly absorbed preparations: 30 minutes for analgesic and antipyretic effects.

Rectal suppositories: 1–2 hours for antipyretic effects.

Continuous oral therapy: 1–4 days for anti-inflammatory effect.

Food

Food decreases rate but not extent of absorption; peak plasma concentrations of aspirin and salicylate may be decreased.

Plasma Concentrations

Plasma salicylate concentrations of 30–100 mcg/mL produce analgesia and antipyresis; the concentration required for anti-inflammatory effect is 150–300 mcg/mL; toxicity noted at 300–350 mcg/mL.

Steady-state plasma salicylate concentrations increase more than proportionally with increasing doses as a result of capacity-limiting processes.

Special Populations

During the febrile phase of Kawasaki disease, oral absorption may be impaired or highly variable.

Distribution

Extent

Widely distributed; aspirin and salicylate distribute into synovial fluid. Crosses placenta and distributed into milk.

Plasma Protein Binding

Aspirin: 33%.

Salicylate: 90–95% bound at plasma salicylate concentrations <100 mcg/mL; 70–85% bound at concentrations of 100–400 mcg/mL; 25–60% bound at concentrations >400 mcg/mL.

Elimination

Metabolism

Partially hydrolyzed to salicylate by esterases in the GI mucosa. Unhydrolyzed aspirin subsequently undergoes hydrolysis by esterases mainly in the liver but also in plasma, erythrocytes, and synovial fluid.

Salicylate is metabolized in the liver by the microsomal enzyme system.

Elimination Route

Excreted in urine via glomerular filtration and renal tubular reabsorption as salicylate and its metabolites. Urinary excretion of salicylate is pH dependent; as urine pH increases from 5 to 8, urinary excretion of salicylate is greatly increased.

Half-life

Aspirin: 15–20 minutes.

Half-life of salicylate increases with increasing plasma salicylate concentrations.

Salicylate: 2–3 hours when aspirin administered in low doses (325 mg).

Salicylate: 15–30 hours when aspirin administered in higher dosages.

Special Populations

Salicylate and its metabolites readily removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.

Stability

Storage

Oral

Capsules

Aspirin in fixed-combination with extended-release dipyridamole: 25°C (may be exposed to 15–30°C). Protect from excessive moisture.

Gum

15–25°C; protect from excessive moisture.

Tablets

Room temperature (Bayer products, excluding Alka-Seltzer^® products); avoid high humidity and excessive heat (40°C).

15–30°C (Easprin^®).

20–25°C (Anacin^® Extra Strength); protect from moisture.

Protect from excessive heat (Alka-Seltzer^® products).

Rectal

Suppositories

2–15°C.

Actions

• Inhibits COX-1 and COX-2 activity.
• Pharmacologic actions similar to those of prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.
• Irreversibly acetylates and inactivates COX-1 in platelets.
• The existence of 2 COX isoenzymes with different aspirin sensitivities and extremely different recovery rates of their COX activity following inactivation by aspirin at least partially explains the different dosage requirements and durations of aspirin effects on platelet function versus the drug’s analgesic and anti-inflammatory effects.
• Effects on urinary excretion of uric acid are dose related; large dosages (e.g., 1.3 g 4 times daily) enhance urinary excretion and decrease serum concentrations of uric acid , intermediate dosages (e.g., 650 mg to 1 g 3 times daily) usually do not alter uric acid excretion, and low dosages (e.g., <325 mg 3 times daily) inhibit excretion and may increase serum uric acid concentrations.