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标题：Bacampicillin Uptake Is Shared with Thiamine in Caco-2 Cells
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作者：Masako Oda ; Kaori Fujimoto ; Michiya Kobayashi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：7
页码：1344-1349
DOI：10.1248/bpb.30.1344
出版社：The Pharmaceutical Society of Japan
摘要：Bacampicillin was developed as a prodrug to improve the intestinal absorption of its metabolite ampicillin. This study was undertaken to characterize bacampicillin transport in Caco-2 cells. The uptake of bacampicillin in Caco-2 cells was significantly greater than those of ampicillin and pivampicillin. An Eadie–Hofstee plot obtained from 5-min uptake of 0.2—5 m M bacampicillin was linear, indicating the presence of a saturable transport system for bacampicillin with K _m and V _max of 3.6 m M and 23.9 nmol/mg protein/min, respectively. Hydrophilic organic cations such as choline, cimetidine, guanidine, nicotinamide, 1-methylnicotiamide, and tetraethylammonium failed to modulate bacampicillin uptake in Caco-2 cells whereas diphenhydramine, procainamide, and thiamine significantly depressed it. Moreover, when thiamine was preloaded in Caco-2 cells, bacampicillin uptake was significantly increased, indicating that this cationic vitamin was capable of trans -stimulating bacampicillin transport across the apical membrane of Caco-2 cells. However, trans -stimulated bacampicillin uptake was not observed in the presence of diphenhydramine. Bacampicillin uptake increased with elevation of the medium pH, and the known modulators of thiamine transport such as amiloride and oxythiamine significantly inhibited bacampicillin uptake. Thiamine also significantly decreased the apical-to-basolateral transport of bacampicillin across Caco-2 cell monolayers. However, thiamine did not exert any modulating effect on pivampicillin uptake and its apical-to-basolateral permeation in Caco-2 cells. These results suggest that bacampicillin is transported in Caco-2 cells, sharing a carrier-mediated system with thiamine.
关键词：bacampicillin;pivampicillin;prodrug;carrier-mediated transport;thiamine;Caco-2 cell