Effect of Side Chains Including the N-Methyl-tetrazole-thiol Group of β-Lactam Antibiotics on Transport in Cultured Kidney Epithelial Cells LLC-PK_1

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In this study, the transcellular transport characteristics of four β-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK_1,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 influende the transcellular transport behaviors of β-lactam antibiotics. In contrast, cefotiam transport across LLC-PK_1 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 secretoryoriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4℃) 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 β-lactam antibiotics were not correlated to the degree of transcellular transport, directly.
社団法人日本薬学会の論文
1998-10-15