著者

KITAGAWA Shuji SUGAYA Yoshio

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.19, no.2, pp.268-273, 1996-02-15

参考文献数

34

被引用文献数

4 1

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Characteristics of transport of an oral aminocephalosporin, cefroxadine, in rabbit small intestinal brush border membrane vesicles were examined. Uptake rate of cefroxadine was saturable in the presence of an inward H<SUP>+</SUP> gradient, and kinetic parameters were similar to those of cephradine. However, the uptake rate was almost linear with the concentration in the absence of an inward H<SUP>+</SUP> gradient up to 5mM. Overshoot phenomenon was observed in the presence of an inward H<SUP>+</SUP> gradient at 37°C, but it disappeared with decrease of temperature. The Arrhenius plot of uptake rate constant showed a break point at approximately 30°C. Cefroxadine uptake was optimum in the vicinity of pH 5.5 at 37°C, but the dependence on extravesicular pH disappeared at 15°C. The uptake of cefroxadine in the presence of an inward H<SUP>+</SUP> gradient was markedly inhibited by other aminocephalosporins such as cephalexin, but the inhibition was only slight in the absence of an inward H<SUP>+</SUP> gradient. Alkyl alcohols such as n-hexyl alcohol also inhibited H<SUP>+</SUP>-coupled uptake of cefroxadine at the concentration range at which the alcohols increased the membrane fluidity, and overshoot phenomenon diminished, suggesting that H<SUP>+</SUP>-coupled transport of cefroxadine is sensitive to the alcohol-induced increase in membrane fluidity. On the other hand, the alcohols rather stimulated its uptake in the absence of an H<SUP>+</SUP> gradient.