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The ability of phenothiazines to enhance the rectal absorption of sodium cefoxitin and gentamicin sulphate from aqueous formulations was examined in rats. In the absence of absorption-promoting adjuvants, sodium cefoxitin and gentamicin sulphate bioavailabilities from the rectal compartment were less than 5% of the corresponding intravenous administration. In aqueous microenemas containing 20 mg ml-1 phenothiazine, sodium cefoxitin bioavailability increased to 16-62%, while gentamicin sulphate bioavailability increased to 74-146%. The absorption-promoting potential of chlorpromazine and perphenazine was concentration-dependent, with significant increases in gentamicin sulphate absorption occurring with 1 mg ml-1 chlorpromazine or 2.5 mg ml-1 perphenazine. Maximal gentamicin sulphate bioavailability and serum concentrations were achieved with 10 mg ml-1 chlorpromazine or 20 mg ml-1 perphenazine. The findings indicate that the phenothiazines, which are well absorbed rectally, also significantly enhance the rectal absorption of water-soluble, poorly absorbed compounds.

The absorption of cefoxitin from rat intestine, rectum and small intestine was greater when the powdered form was administered than when an aqueous solution was given. Cefoxitin absorption from the small intestine was significantly increased after its administration in suppository form prepared with a triglyceride base, although rectal absorption from the suppository did not differ from that of the drug in powdered form. The increase in absorption by the small intestine from the suppository form may be due to fatty acids produced from triglyceride by lipase.

Sodium salicylate, disodium ethylenediaminetetraacetic acid (EDTA) and polyoxyethylene-23-lauryl ether (POE) significantly enhanced the absorption of cefoxitin from the rectum but with the following differences. The effectiveness of salicylate or EDTA was enhanced by sodium chloride, whereas the activity of POE was not. Although the ratios of plasma cefoxitin peak values to cefoxitin dose were constant with POE or EDTA, the peak to dose ratios with salicylate decreased with increasing cefoxitin concentration. Phlorizin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) inhibited the effectiveness of salicylate, but did not influence the adjuvant action of either POE or EDTA. Although treatment with salicylate resulted in slightly less protein release than treatment with NaCl, both POE and EDTA increased the release of protein from the rectal mucosa. It appears that the effects of salicylate occur at the protein fraction of the rectal mucosa through a saturable process whereas the adjuvant action of POE and EDTA appears to involve some irreversible disruption of the membrane.

Lymphatic uptake of sodium cefoxitin after injection into rectal connective tissue was greater than after injection into the femoral muscle of rats. Coadministration with sodium 5-methoxysalicylate enhanced lymphatic drug uptake at both sites. This enhancement may be an indirect result of 5-methoxysalicylate's suppression of vascular permeation of the cefoxitin. An adjuvant-induced increase in lymphatic fluid flow may also be partially involved in the enhancement of cefoxitin lymphatic transport.