Clinical pharmacokinetics of salicylates: a re-assessment

1 Aspirin is partly hydrolyzed to salicylic acid during absorption. Absorbed aspirin is rapidly hydrolyzed systemically. Salicylic acid elimination kinetics are dependent on drug concentration due to the limited capacity of two major biotransformation pathways: formation of salicyluric acid and of salicylphenolic glucuronide. 2 The time courses of the various pharmacological effects of single doses of aspirin are not directly coincident with the plasma concentrations of either aspirin or salicylic acid but there is reasonably good evidence that the pharmacological effects are related to the concentration of aspirin, salicylic acid, or both. 3 Steady-state plasma salicylate concentrations increase more than proportionally with increasing daily dose; the time required to reach steady state increases with increasing daily dose. Dosage intervals of 8 or even 12 h are usually sufficient to maintain plasma salicylate concentrations in the anti-inflammatory concentration range. Monitoring of plasma salicylate concentrations in this range is facilitated by the relatively small drug concentration fluctuations during a dosing interval at steady-state. 4 Limited data suggest that the pharmacological activity of salicylate is produced by free (unbound) drug. As the plasma protein binding of salicylic acid is concentration-dependent and subject to pronounced interindividual differences, it is preferable, at least in principle, to monitor free rather than total concentrations of salicylate in plasma. Although salicylate concentration in saliva reflects the free rather than total salicylate concentration in plasma or serum, use of saliva for indirect monitoring of plasma salicylate concentrations seems to be impractical for technical reasons.