title: Modification of ceftibuten transport by the addition of non-ionic surfactants.
abstract: The effects of non-ionic surfactants on the carrier-mediated transport of ceftibuten by rat intestinal brush-border membrane vesicles (BBMVs) were investigated. Ceftibuten uptake by BBMVs was measured by a rapid filtration technique. The concentration of surfactants for the uptake experiments was determined by a decrease in the turbidity of BBMV suspension and by the release of an impermeable probe, 2',7'-bis(carboxyethyl)-4(5)-carboxyfluorescein, from the vesicle inside. In fact, the surfactant concentration of 0. 03% (w/v) was selected to maintain the stability of BBMVs. The extent of ceftibuten uptake by BBMVs with various surfactants was correlated with their physicochemical properties, i.e. hydrophile-lipophile balance (HLB), critical micelle concentration (c.m.c.), average diameter of micelle colloid, and polydispersity determined by particle size distribution. The surfactants used were divided into two groups on the basis of polydispersity index (d(w)/d(n)), i.e. low polydispersity (d(w)/d(n) congruent with1) and high polydispersity d(w)/d(n)2). The ceftibuten uptake due to the addition of surfactants with low polydispersity increased with a decrease in the HLB number. These results indicate that the ceftibuten transport is modulated by the size distribution and hydrophobicity of surfactants. In addition, the effects of surfactants on the membrane lipid fluidity monitored by diphenylhexatriene (DPH) and trimethylammonium diphenylhexatriene (TMA-DPH) were investigated. There was significant correlation between ceftibuten uptake and the fluorescence anisotropy of TMA-DPH-labeled membranes due to the addition of surfactants with low polydispersity (r=-0.81, P<0.0001). These results suggest that surfactants with low polydispersity, in part, increase or decrease the outer membrane leaflet, thereby enhancing or suppressing the ceftibuten transport by BBMVs, and that ceftibuten transport caused by surfactants with low polydispersity may be strongly dependent on the hydrophobic interaction.
authors.affiliation: Division of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. k-koga@hokuriku-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Koga
authors.forename: T
authors.initials: T
authors.lastname: Ohyashiki
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: S
authors.initials: S
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D000077722:Ceftibuten; D002511:Cephalosporins / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D002511:Cephalosporins; D008563:Membrane Lipids; D008565:Membrane Proteins; D013501:Surface-Active Agents; D000077722:Ceftibuten