Clinical Pharmacokinetics of Aspirin and Other Salicylates: Implications for Research and Therapy.
Abstract:Aspirin undergoes substantial presystemic hydrolysis to salicylic acid following oral administration. Pronounced and apparently consistent interindividual differences in the magnitude of this effect must be taken into consideration in the design of studies to assess the usefulness of aspirin for the prevention of transient cerebral ischemia, stroke, and myocardial infarction. Salicylic acid, which is apparently responsible for the anti-inflammatory effect of aspirin, is subject to capacity-limited elimination due to saturation of two biotransformation pathways, namely formation of salicyluric acid (i.e., conjugation with glycine) and of salicyl phenolic glucuronide. Consequently, the following changes occur as the maintenance dose of a salicylate is increased: steady-state body levels increase more than proportionally, the time to reach steady state increases, and the effects of changes in urinary pH (which affect the renal clearance of salicylic acid) on the body clearance of salicylate become more pronounced. These factors must be taken into consideration in the design of aspirin dosage regimens and in the monitoring and interpretation of plasma salicylate concentrations.
Document Type: Research Article
Publication date: 1981-03-01
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