Rapid Establishment of Therapeutic Serum Concentrations of Salicylates

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Abstract
A minimum serum salicylate concentration of 150 .mu.g/ml is required to control certain inflammatory disease processes. A loading regimen designed to rapidly achieve this minimal level was evaluated in 6 normal volunteers (age 22-27 yr, weight 70.5-84.1 kg) using a randomized crossover design. The control group received 650 mg aspirin (ASA) every 4 h for 48 h. The loading regimen was 2600 mg ASA divided into 2 equal doses 4 h apart. Maintenance dosing of 650 mg ASA every 4 h was then started 4 h after the completion of the loading regimen and continued for 40 h. Serum samples were drawn at 0, 2, 4, 6, 8, 12, 24, 36 and 48 h after initiation of the study and were assayed for salicylate concentration by UV spectrophotometry. Loading with aspirin produced serum concentrations which were significantly higher (P < 0.01) for the first 24 h and reduced the time to reach 150 .mu.g/ml (15.3 .+-. 5.9 h vs. 30.4 .+-. 8.65 h, P < 0.001) for 5 of 6 subjects when compared to a conventional regimen. One subject did not achieve 150 .mu.g/ml at 48 h with either regimen. Considerable intersubject variation in serum concentration was noted at 48 h for both regimens. A loading regimen for aspirin may have utility for patients in whom rapid attainment of a therapeutic antiinflammatory serum concentration is desirable.

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