Interaction of aspirin with nonsteroidal anti-inflammatory drugs in rats

Mielens, Z.E.; Drobeck, Hans P.; Rozitis, Janis; Sansone, Vito

doi:10.1111/j.2042-7158.1968.tb09807.x

Cited by 31 publications

(6 citation statements)

References 9 publications

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“…Rightly or wrongly non-steroidal anti-inflammatory drugs are commonly prescribed in combinations in the treatment of rheumatoid arthritis (Grennan, Karetai & Palmer, 1977). Most previous studies regarding potential interactions between antiinflammatory drugs given concurrently in both animals (Kaiser & Glenn, 1974;Mielens, Drobeck, Rozitis & Sansone, 1968) and in man (Brooks, Walker, Bill, Buchanan & Rhymer, 1975) suggest that little synergism occurs. However, one recent study has demonstrated that the combination of naproxen and salicylates in patients with rheumatoid arthritis may produce a synergistic effect (Wilkins & Segre, 1976).…”

Section: Introduction Methodsmentioning

confidence: 98%

The aspirin‐ibuprofen interaction in rheumatoid arthritis.

Dm¹,

Ferry²,

Ashworth³

et al. 1979

Brit J Clinical Pharma

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1 This was a double‐blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis. Two dosage regimes were tested. 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate (1600 mg ibuprofen and 3.6 g aspirin daily) but not low (800 mg ibuprofen and 2.4 g aspirin daily) dosages of both drugs. 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial. 4 No consistent effect of ibuprofen administration on serum salicylate levels was found. 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half‐ lives of the drug.

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Section: Introduction Methodsmentioning

confidence: 98%

The aspirin‐ibuprofen interaction in rheumatoid arthritis.

Dm¹,

Ferry²,

Ashworth³

et al. 1979

Brit J Clinical Pharma

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“…The most thoroughly documented of these is the interaction between indomethacin and aspirin in the rat; there is less extensive documentation for other pairs of drugs. 10,16,17 With naproxen and aspirin, a similar situation obtains. 1 Such a naproxen-aspirin interaction is possible in man and, if confirmed, could well have clinical implications.…”

mentioning

confidence: 83%

Naproxen‐aspirin interactions in man

Segre¹,

Chaplin²,

Forchielli³

et al. 1974

Clin Pharma and Therapeutics

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Pharmacokinetic interactions between aspirin and other nonsteroidal anti‐inflammatory drugs, including naproxen, have been demonstrated in experimental animals. This study shows that simultaneous oral administration of aspirin and naproxen in man results in a small but statistically significant lowering of plasma levels of naproxen. This effect is not mediated by competition for drug absorption but is associated with enhanced renal clearance of naproxen or its metabolites. Salicylates displace naproxen from binding sites on plasma proteins, a phenomenon that may be responsible for the accelerated clearance. The clinical significance, if any, Of these findings is not yet established, but the relatively small magnitude of the effects noted suggests that the likelihood of a meaningful interaction is small.

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“…cluded from comparative trials of nonsteroidal antiinflammatory agents (1 6,17 ity of fenoprofen in treating rheumatoid arthritis patients receiving aspirin can only complicate an already complicated field of endeavor. These considerations and the unresolved controversy about an aspirin-indomethacin interaction led us to study the effect of aspirin on indomethacin concentrations in plasma under conditions similar to those described for the aspirin-fenoprofen interaction.…”

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confidence: 99%

Interactions of aspirin with nonsteroidal antiinflammatory drugs in man

Rubin

Rodda

Warrick

et al. 1973

Arthritis & Rheumatism

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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.

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Interaction of aspirin with nonsteroidal anti-inflammatory drugs in rats

Cited by 31 publications

References 9 publications

The aspirin‐ibuprofen interaction in rheumatoid arthritis.

The aspirin‐ibuprofen interaction in rheumatoid arthritis.

Naproxen‐aspirin interactions in man

Interactions of aspirin with nonsteroidal antiinflammatory drugs in man

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