Healthy volunteers ingested fenoprofen and indomethacin, each alone or combined with aspirin. Concentrations in plasma of both fenoprofen and indomethacin were reduced significantly when administered with aspirin. Reduction of fenoprofen concentrations depended on the aspirin dosage and occurred whether fenoprofen was administered orally or intravenously. Fenoprofen did not affect plasma concentrations of salicylates. These results emphasize the need to assess carefully the effects of salicylates in comparative clinical trials of nonsteroidal antiinflammatory agents.We have reported on the physiologic disposition in man of fenoprofen, a new antiinflamrnatory, antipyretic analgesic (1-4). In accord with thespecial place that aspirin holds in the treatment of rheumatoid arthritis, the coadministration of aspirin or other aryl acid compounds is probable in the management of this disease. Recent studies using '4C-labeled indomethacin indicated that salicylates lowered plasma concentrations of indomethacin in rats ( 5 ) and man (6). Others, however, using spectrofluorometric assays for indomethacin and its metabolites, have not observed this aspirin effect in man (7). Regardless, it was the clinical impression of one of us (ASR) that arthritic patients receiving fenoprofen alone had a better response than when they received fenoprofen and aspirin together. These factors, coupled with the continuing practice of administering aspirin when evaluating the effects of nonsterodial antiinflammatory compounds, prompted us to investigate the effects of aspirin on fenoprofen and indomethacin concentrations in human plasma, and effects of aspirin on the urinary excretion of fenoprofen and its metabolites. MATERIALS AND METHODS Analytical MethodsUrine samples were collected without preservatives and frozen until assay. Blood samples were drawn by venipuncture into heparinized tubes; plasma was decanted after centrifugation and frozen until assay.Total dialyzable salicylate in plasma was measured by fluorescence (8,9). Fenoprofen and its metabolites did not interfere with the assay for salicylate.Fenoprofen and fenoprofen metabolites were measured in extracts of plasma and urine by gas liquid chromatography. This method involves extraction of the drug (and metabolites), formation of silyl derivatives, and injection into 4-foot glass columns containing 3.8% UCCW982 on Diatoport-S (2, 10). Aspirin and salicylic acid did not interfere with the assays for fenoprofen or its metabolites.Indomethacin was measured spectrofluormetrically in plasma (1 1). Salicylates, which might interfere with the analysis, were removed by washing the plasma extracts with citrate buffer.

To establish therapeutic guidelines, benoxaprofen kinetics were examined in 26 adult subjects with normal and decreased renal function. Mean peak plasma concentrations after a single 600-mg dose ranged from 58 to 72 mg/l, independent of renal function. Elimination half-life and benoxaprofen plasma clearance correlated with creatinine clearance. Hemodialysis did not remove benoxaprofen from plasma. A dosage nomogram was derived from which a dose one half of the normal maintenance dose was suggested for patients with severe renal failure.

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