title: Rapid establishment of therapeutic serum concentrations of salicylates.
abstract: A minimum serum salicylate concentration of 150 microgram/ml is required to control certain inflammatory disease processes. A loading regimen designed to rapidly achieve this minimal level was evaluated in six normal volunteers (age 22 to 27 years, weight 70.5 to 84.1 kg) using a randomized crossover design. The control group received 650 mg aspirin (ASA) every 4 hours for 48 hours. The loading regimen was 2600 mg ASA divided into two equal doses 4 hours apart. Maintenance dosing of 650 mg ASA every 4 hours was then started 4 hours after the completion of the loading regimen and continued for 40 hours. Serum samples were drawn at 0, 2, 4, 6, 8, 12, 24, 36, and 48 hours 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 less than 0.01) for the first 24 hours and reduced the time to reach 150 microgram/ml (15.3 +/- 5.9 hours versus 30.4 +/- 8.65 hours, P less than 0.001) for five of six subjects when compared to a conventional regimen. One subject did not achieve 150 microgram/ml at 48 hours with either regimen. Considerable intersubject variation in serum concentration was noted at 48 hours for both regimens. We suggest that a loading regimen for aspirin may have utility for patients in whom rapid attainment of a therapeutic antiinflammatory serum concentration is desirable.
mesh_terms: D000328:Adult; D006801:Humans; D012459:Salicylates / Q000009:adverse effects / Q000097:blood*; D013997:Time Factors; D014012:Tinnitus / Q000139:chemically induced
chemical_list: D012459:Salicylates