Interactions of aspirin with nonsteroidal antiinflammatory drugs in man

Abstract

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.

Interaction of isoxicam with acetylsalicylic acid.

“…In the absence of ASA, the kinetic disposition of a single dose of isoxicam in this group of normal volunteers revealed a long appearance t,i, of 2.5 h, a delayed time to peak concentration (10 h) and a slow disappearance t½ of 31 h similar to the results of a previous investigation (Accardo et al, 1983 (Jeremy & Towson, 1970;Rubin et al, 1973) whereas others failed to find an effect (Champion et al, 1971;Brooks et al, 1975). Concurrent administration of ASA decreased the plasma protein binding of ketoprofen and increased its plasma clearance at steady state (Williams et al, 1981).…”

Management of Hyperuricemia and Gout

“…At the doses of ibuprofen and ketoprofen used in gout, warfarin is displaced from its binding site on plasma proteins resulting in increased anticoagulant effects [ 119,157 ] . Similar effects are observed with naproxen [158][159][160][163][164][165] . In addition, patients taking anticoagulants are at increased risk of bleeding generally, and anticoagulants increased the risks of NSAID-induced bleeding from the upper GI tract in particular.…”

Absorption and excretion of tolmetin in arthritic patients

“…1) is an anti-inflammatory drug which is both efficacious and safe in the treatment of rheumatoid arthritis (RA).3, 4,6,7,9 The biotransformation of tolmetin in man and animals has been reported 12 and shown to include oxidation of the aromatic methyl group to form I-methyl-5-(4-carboxybenzoyI)-IH -pyrrole-2-acetic acid (MCPA) (Fig. 1) and conjugation with glucuronic acid to form an acyl glucuronide.…”