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Pharmacokinetic monitoring of salicylate therapy in children with juvenile rheumatoid arthritis.

Free and total (sum of free and protein bound) salicylate concentrations in serum were determined in 17 children (age: 4-17 years) with definite juvenile rheumatoid arthritis. These measurements were carried out immediately before and 2, 4, and 8 hours after the morning dose during a strict 8 hourly aspirin treatment regimen (regular tablets) started 5 days earlier. The ratio of the 0 to 8 hour total salicylate concentrations was 0.95 +/- 0.10 (mean +/- SD), indicating that steady state had been attained. The ratio of the maximum to minimum concentrations during the dosing interval ranged from 1.05 to 2.26 and decreased with increasing average concentration. The concentration ratio was less than 1.3 at average salicylate concentrations above 20 mg/100 ml. It is concluded that the timing of a blood sample is not critical for monitoring steady state serum salicylate concentrations in the usual therapeutic range if the dosing interval is 8 hours or less. Free salicylate concentrations increased more than proportionately with increasing total concentrations due to the concentration dependent protein binding of the drug in serum.