title: Effect of chlorpromazine on the permeability of beta-lactam antibiotics across rat intestinal brush border membrane vesicles.
abstract: The effect of chlorpromazine on the membrane permeability of beta-lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D-glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25 degrees C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D-glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of beta-lactam antibiotics and actively transported substances in a different manner.
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iseki
authors.forename: M
authors.initials: M
authors.lastname: Sugawara
authors.forename: H
authors.initials: H
authors.lastname: Saitoh
authors.forename: K
authors.initials: K
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Arita
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006033:Glycylglycine / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D006033:Glycylglycine; D005947:Glucose; D002746:Chlorpromazine