The promoting action of the calcium chelating compound EDTA on intestinal drug absorption is supposed to be based on Ca2+ depletion, inducing widening of tight junctions. The aim of the present study was to evaluate the effects of the calcium-binding agent 3-amino-1-hydroxypropylidene-1,1-diphosphonate disodium salt (APD) on rectal cefoxitin absorption in rats. The extent of rectal cefoxitin absorption was enhanced by 0.5 to 6% w/v of APD, on rectal infusion as well as on bolus delivery, the latter regimen tending to result in lower bioavailabilities. A maximal cefoxitin bioavailability of 85 +/- 10% was achieved by infusion with 4% w/v of APD, compared with 14 +/- 12% without APD.