title: Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1.
abstract: In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid. There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics. In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction. It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol. The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent. These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam. The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly.
authors.affiliation: Department of Pharmacy, Tonan Hospital, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: M
authors.initials: M
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Nishida
authors.forename: M
authors.initials: M
authors.lastname: Takada
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport; D015281:Cefmenoxime / Q000737:chemistry / Q000493:pharmacokinetics*; D015311:Cefmetazole / Q000737:chemistry / Q000493:pharmacokinetics*; D002439:Cefotaxime / Q000737:chemistry / Q000493:pharmacokinetics*; D015310:Cefotiam / Q000737:chemistry / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D018374:LLC-PK1 Cells; D013329:Structure-Activity Relationship; D013552:Swine; D013777:Tetrazoles / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013777:Tetrazoles; C038625:1-N-methyl-5-thiotetrazole; D015311:Cefmetazole; D015310:Cefotiam; D015281:Cefmenoxime; D002439:Cefotaxime