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.
Sutton
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INTERx Research Corporation, MSDRL, Lawrence, Kansas 66047.
LeCluyse
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Cammack
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D000277:Adjuvants, Pharmaceutic; D000818:Animals; D001682:Biological Availability; D002440:Cefoxitin / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013535:Suspensions
D000277:Adjuvants, Pharmaceutic; D013535:Suspensions; D010172:Palmitoylcarnitine; D002440:Cefoxitin