Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat.
A means of enhancing absorption of the antibiotic, fosfomycin, has been investigated using promoters in rat jejunum and colon. Polyoxyethylene lauryl ether (BL-9EX), saponin, the sodium salts of fatty acids and mixed micelles were effective at 1% in increasing fosfomycin absorption. Of the sodium salts of saturated medium-chain fatty acids examined, the strength of this effect was in the order caprate greater than laurate greater than caprylate. Mixed micelles, consisting of fusogenic lipids and sodium taurocholate, enhanced fosfomycin absorption independently of the degree of unsaturation of the lipids; their effectiveness far exceeded that of sodium taurocholate alone. The action of these promoters was more evident in the colon than in the jejunum, except for the sodium salts of bile acids and disodium ethylenediaminetetraacetate (EDTA-2Na). The effects of glycocholate and taurocholate were essentially the same at both absorption sites, but that of EDTA-2Na was much greater in the jejunum than the colon. Improved fosfomycin absorption was observed at more than 0.5% sodium caprate concentrations in both the jejunum and colon. BL-9EX was effective at 0.1% in the jejunum or at 0.05% in the colon. The effectiveness at these low concentrations demonstrates the practicality of promoters for improving fosfomycin absorption with only minor membrane damage, especially in the colon.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D005578:Fosfomycin / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008823:Micelles; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012503:Saponins / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*
D001647:Bile Acids and Salts; D003902:Detergents; D005227:Fatty Acids; D008823:Micelles; D012503:Saponins; D013501:Surface-Active Agents; D000077423:Polidocanol; D005578:Fosfomycin; D011092:Polyethylene Glycols