caa a22 4500 477127894 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012113430539 doi (NATIONALLICENCE)springer-10.1023/A:1012113430539 Restricted Intestinal Absorption of Some β-Lactam Antibiotics by an Energy-Dependent Efflux System in Rat Intestine [Elektronische Daten] [Hiroshi Saitoh, Hiroko Fujisaki, Bruce Aungst, Katsumi Miyazaki] Purpose. The purpose of this study was to examine factors limiting the intestinal absorption of orally inactive β-lactam antibiotics. Methods. Permeation behaviors of various β-lactam antibiotics across rat intestinal segments were evaluated in vitro using diffusion cells. Results. Poorly absorbed β-lactam antibiotics, like cephaloridine and cefoperazone, commonly exhibit greater serosal-to-mucosal permeation than mucosal-to-serosal permeation, while cephalexin permeation was greater in the mucosal-to-serosal direction. In the absence of D-glucose, secretory-oriented permeation of cephaloridine and cefoperazone disappeared. Addition of sodium azide into an experimental buffer including D-glucose significantly and selectively enhanced mucosal-to-serosal permeation of cephaloridine and cefoperazone. Although benzylpenicillin, ampicillin, and amoxicillin all showed secretory-oriented permeation, the tendency to permeation was greatest with benzylpenicillin and least with amoxicillin. Probenecid stimulated mucosal-to-serosal permeation of cephaloridine, but verapamil and p-aminohippuric acid had no significant effect on it. Conclusions. It has been suggested that mechanisms which induce secretory-oriented permeation of orally inactive β-lactam antibiotics are factors limiting intestinal absorption of such antibiotics. This energy-demanding efflux system was distinct from P-glycoprotein-mediated transport. A free α-amino group in the molecule is an important factor for reducing an affinity with the efflux system. Plenum Publishing Corporation, 1997 β-lactam antibiotics nationallicence intestinal efflux nationallicence α-amino group nationallicence restricted absorption nationallicence Saitoh Hiroshi Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut Fujisaki Hiroko Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut Aungst Bruce DuPont Merck Research Laboratories, 19880-0400, Wilmington, Delaware aut Miyazaki Katsumi Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 645-649 0724-8741 14:5<645 1997 14 11095 https://doi.org/10.1023/A:1012113430539 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012113430539 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Saitoh Hiroshi Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Fujisaki Hiroko Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Aungst Bruce DuPont Merck Research Laboratories, 19880-0400, Wilmington, Delaware aut NATIONALLICENCE 700 1- Miyazaki Katsumi Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-Ku, 060, Sapporo, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 645-649 0724-8741 14:5<645 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer