Enhanced bioavailability of cefoxitin using palmitoyl L-carnitine. I. Enhancer activity in different intestinal regions.

The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3 mg/rat, pH 4.0) enhanced cefoxitin bioavailability (F) by 0-, 22-, 16-, and greater than 32-fold in the duodenum, jejunum, ileum, and colon regions, respectively. The inability of PCC to improve F in the duodenum could not likely be attributed to enzymatic degradation of the enhancer, since coadministration with protease and esterase inhibitors produced similar results (F = 30%). Coadministration of PCC solution with cefoxitin in the unligated or ligated colon, increased F to 33 and 76%, respectively. Qualitatively similar results were seen with PCC suspensions (3 mg/rat, pH 6.0). Maintaining a high concentration of cefoxitin and PCC in a restricted region (i.e., by ligating a 2- to 3-cm section of the colon) afforded a two- to threefold advantage over an unligated colon section. The difference in cefoxitin bioavailability between ligated and unligated colon was probably due to sample spreading and subsequent/simultaneous dilution.

Influence of ionic strength on rectal absorption of gentamicin sulfate in the presence and absence of sodium salicylate.

The rectal absorption of gentamicin sulfate in rats, both in the presence and absence of sodium salicylate, was facilitated by the use of high ionic strength aqueous formulations. The relative order of effectiveness in promoting gentamicin absorption was sodium dihydrogen phosphate congruent to sodium chloride much greater than potassium chloride, indicating a preferential effect of sodium ions. The increased gentamicin bioavailability in response to sodium salicylate adjuvant activity appeared to be independent of and additive to the increased gentamicin absorption due to high ionic strength conditions. The inability of sorbitol to increase gentamicin bioavailability above control levels indicated that elevated osmotic pressure was not a major determinant of rectal gentamicin absorption.

Involvement of active sodium transport in the rectal absorption of gentamicin sulfate in the presence and absence of absorption-promoting adjuvants.

The involvement of active sodium transport in the rectal absorption of gentamicin sulfate was examined in rats, employing aqueous microenemas of known total ionic strength (mu) in the presence or absence of absorption-promoting adjuvants. Rectal gentamicin bio-availability, which is negligible (1 +/- 1.2%) at an ionic strength of 0.15 without adjuvants, is significantly (p less than 0.01) increased by including adjuvants in the formulation (sodium salicylate, 12 +/- 4.0%; sodium-5-bromosalicylate, 59 +/- 15.1%; disodium ethylene (dinitrilo)tetraacetate, 24 +/- 9.3%). Pretreating the rectal mucosa cells with ouabain, a specific inhibitor of active sodium transport, significantly (p less than 0.01) reduced gentamicin absorption in response to all three adjuvants. In contrast to previous findings with sodium chloride, high ionic strength choline chloride (mu = 1.056) did not promote gentamicin absorption. The data indicate that active sodium transport is an integral component of rectal absorption of water-soluble compounds and may be involved in the mechanism of action of absorption-promoting adjuvants.