The synergistic effects of concurrent administration to rats of EDTA and sodium salicylate on the rectal absorption of sodium cefoxitin and the effects of inhibitors

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Abstract
Plasma levels of cefoxitin, as enhanced by rectal coadministration of sodium salicylate, were reduced by concurrent administration of <0.5 mg mL−1 N-ethylmaleimide (NEM) or p-chloromercuriphenylsulphonic acid, sodium salt (p-CMP). Concentrations of these inhibitors above 1 mg mL−1 resulted in enhanced peak plasma values of cefoxitin. This did not occur after coadministration with either ethylenediaminetetraacetic acid (EDTA) or polyoxyethylene-23 lauryl ether (POE). Ouabain and 2,4-dinitrophenol (DNP) suppressed plasma cefoxitin levels in the presence of salicylate and the enhancing effects of EDTA and POE when EDTA and POE were administered at low doses. At higher concentrations of EDTA and POE, DNP had little effect, while ouabain had little effect on POE and only partially suppressed the effects of EDTA. Plasma concentrations of cefoxitin after coadministration with salicylate and POE together, or with EDTA and POE together, were about the same as expected from summing the plasma levels resulting from coadministration of each adjuvant individually at the same concentrations. However, combined administration of salicylate and EDTA with cefoxitin yielded plasma cefoxitin concentrations which were much higher than expected from the sum of their individual actions.