Characteristics of Uptake of Cefroxadine by Rabbit Small Intestinal Brush Border Membrane Vesicles

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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⁺ 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⁺ gradient up to 5mM. Overshoot phenomenon was observed in the presence of an inward H⁺ 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⁺ gradient was markedly inhibited by other aminocephalosporins such as cephalexin, but the inhibition was only slight in the absence of an inward H⁺ gradient. Alkyl alcohols such as n-hexyl alcohol also inhibited H⁺-coupled uptake of cefroxadine at the concentration range at which the alcohols increased the membrane fluidity, and overshoot phenomenon diminished, suggesting that H⁺-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⁺ gradient.