Interaction of Salicylates and other Non‐steroidal Anti‐inflammatory Agents in Rats as Shown by Gastro‐ulcerogenic and Anti‐inflammatory Activities, and Plasma Concentrations

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Abstract
The interaction of salicylates and other non-steroidal anti-inflammatory drugs was studied in rats. Concurrent oral administration of sodium salicylate (SS) or salicyclic acid (SA) and indomethacin (IND) significantly reduced the gastro-ulcerogenicity and the plasma concentrations of IND. Acetylsalicylic acid (ASA) failed to do so. IND had no significant influence on plasma concentrations of SA. Simultaneous administration of SS and IND i.p. or s.c. showed the same pattern of interaction as for oral administration. Concurrent oral administration of SS and IND exerted similar anti-inflammatory activity as the single drugs. SS significantly antagonized the ulcerogenicity of ibuprofen and tended to antagonize the ulcerogenicity of ibuprofen and tended to antagonize the ulcerogenic activity of ASA, phenylbutazone, tolfenamic acid and naproxen. In rats SS and SA (but not ASA) evidently interact with IND concerning both gastro-ulcerogenicity and plasma concentrations of IND (but not of SA). The interaction is systemic in nature. The ulcerogenic interaction might be explained partly by the reduced IND plasma concentrations and partly by a weaker inhibition by SS of the prostaglandin system in the rat stomach.