Interactions of cephradine and cefaclor with the intestinal absorption of D-galactose.
Oral cephalosporins are frequently prescribed beta-lactam antibiotics. Although it has been well established that cephalosporins compete with dipeptides for absorption in the intestine, using the same transport mechanism, little is known about the action of the drugs on the absorption of other nutrients. In this work the effect of cephradine and cefaclor on the absorption of D-galactose has been studied. Intestinal sugar uptake was measured in-vitro in pieces of intestine (50 mg) and brush-border membrane vesicles, and in-vivo in intestinal loops. Galactose uptake was inhibited by cephalosporins in a dose-related, time-dependent manner. In-vivo the inhibition appeared when the antibiotics were on the luminal side of the enterocyte and when they reached the gut from the basolateral side. Only the active transport of the sugar was modified; passive transfer did not change in the presence of cephalosporins. In brush-border membrane vesicles, cephradine and cefaclor did not alter sugar uptake in either sodium or potassium gradients. Both antibiotics non-competitively inhibited basolateral Na+,K(+)-ATPase activity. These findings show that cephradine and cefaclor inhibit the active-transport component of galactose absorption because they reduce the activity of the basolateral Na+,K(+)-ATPase.
Idoate
I
I
Departamento de Fisiología y Nutrición, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain.
Mendizábal
M V
MV
Urdaneta
E
E
Larralde
J
J
D000818:Animals; D002433:Cefaclor / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D002515:Cephradine / Q000494:pharmacology*; D004058:Diffusion; D005690:Galactose / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D002511:Cephalosporins; D002433:Cefaclor; D000254:Sodium-Potassium-Exchanging ATPase; D002515:Cephradine; D005690:Galactose