Preparation of controlled-release granules of sodium diclofenac.
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Biomedical subjects
Publications and source records attributed to T Nishihata.
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Concanavalin A (Con A) caused dramatic changes in the structure and function of rat colonic epithelium. The morphological effect was a pronounced, permanent alteration of the microvilli, including fusion and blebbing. The functional change involved an increased permeability to passively transported hydrophilic marker compounds. The functional change was transient in nature. Since coadministration of glucose or mannose inhibited the effect of Con A, the mechanistic effect of Con A probably involves binding to saccharide components of the membrane surface.
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.
Rectal bioavailability of Ara-C (serum AUC 4 h: 65 micrograms h-1 ml-1) administered in a suppository formulation containing tetrahydrouridine (a deamination inhibitor) and sodium salicylate (an adjuvant) to dogs was better than that from a suppository formulation without tetrahydrouridine (serum AUC 4 h: 18 micrograms h-1 ml-1).
Rat colonic absorption of cefmetazole was increased significantly by calmodulin inhibitors such as phenothiazines and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) when they were coadministered at a concentration between 1 and 100 microM. The bioavailability of cefmetazole, determined by area under the blood concentration curve method, increased 20 to 30% by the coadministration of calmodulin inhibitors. It is speculated that the enhancing action of agents on rat colonic absorption of cefmetazole takes place by a paracellular route and coadministration of sodium ion increases their actions.
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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.
Rectal absorption of insulin by depancreatized dogs was significantly enhanced by the coadministration of enamine as a suppository adjuvant and if this was followed by a further suppository containing enamine alone, the insulin absorption was even further enhanced. The additional enamine suppository resulted in high serum insulin concentrations for a longer time and effected a significant decrease in serum glucose concentrations. To decrease serum glucose concentrations effectively in depancreatized dogs, serum insulin levels had to remain high for a long period of time, rather than be transient.
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.
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Experimental observation suggests that the ability of ortho-hydroxybenzoates to alter the permeability of rat rectal epithelial membrane may involve an interaction between the ortho-isomer and the membrane protein. Such an interaction may cause a temporary structural modification of the protein rendering the membrane permeable to compounds normally poorly absorbed from the rectal compartment.
Concanavalin A enhanced the rat rectal absorption of phenol red and cefoxitin at pH 7.4 and the uptake of cefoxitin into brush border membrane vesicles prepared from rat rectal membrane. The enhancing action of concanavalin A demonstrated a sodium ion dependency and was inhibited by the presence of 4,4'-diisothiocyano-2,2'-disulfonate stilbene and phlorizin. This inhibition suggests the involvement of the membrane protein fraction.