H+ coupled transport of orally active cephalosporins lacking an alpha-amino group across brush-border membrane vesicles from rat small intestine.
The effect of an inwardly directed H+ gradient' on the transport characteristics of ceftibuten, cefixime and analogues of ceftibuten in rat intestinal brush-border membrane vesicles have been investigated. In the presence of a transmembrane H+ gradient, ceftibuten and its analogues exhibited a peak to equilibrium overshoot and an accumulation in the vesicles against the concentration gradient. However, the uptake of cefixime and S-1006 [(6R, 7R)-(7-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-8-oxo- 3- carbamoyloxy-methyl-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxyl ic acid), which lacks a carboxyl group at position 4 of carboxyethylidene structure, exhibited no overshoot, although the equilibrium uptake was increased by a H+ gradient. The equilibrium uptake was dependent on the pH of the final incubation medium and the H+ gradient. These data suggested that the orally active cephalosporins were transported into rat intestinal brush-border membrane by the transmembrane H+ gradient and the pH of the medium.
Sugawara
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Japan.
Iseki
K
K
Miyazaki
K
K
D000818:Animals; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077722:Ceftibuten; D002511:Cephalosporins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006859:Hydrogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002511:Cephalosporins; D006859:Hydrogen; D020682:Cefixime; D000077722:Ceftibuten; D002439:Cefotaxime