Sodium and pH Dependent Carrier-Mediated Transport of Antibiotic, Fosfomycin, in the Rat Intestinal Brush-Border Membrane

Takayuki Ishizawa, Akira Tsuji, Ikumi Tamai, Tetsuya Terasaki

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22 Citations (Scopus)


The mechanism of intestinal absorption of an antimicrobial agent, fosfomycin (FOM), was investigated in rats using small intestinal brush-border membrane vesicles (BBMV). The uptake of [3H]FOM by BBMV was osmolarity- and temperature-sensitive and showed apparently saturable uptake kinetics consistent with the Michaelis-Menten equation, having Kt = 15.3 mM and Jmax = 7.78 nmol/30 s/mg protein at 37 °C. An overshoot uptake of FOM was observed in the presence of an inwardly directed Na+ gradient. The replacement of extra vesicular Na+ with choline or mannitol significantly reduced the uptake. An addition of a protonophore, FCCP, significantly decreased the initial uptake of FOM in the absence of Na+ gradient but in the presence of a H+ gradient (pHin = 7.5, pHout = 6.0), whereas in the absence of a H+ gradient no significant difference was observed between the uptakes at an acidic pH (pHin = pHout = 6.0) and a neutral pH (pHin = pHout = 7.5). An inside negative potassium diffusion potential induced by valinomycin enhanced significantly the uptake of FOM. The uptake of FOM in the presence of both Na+- and H+-gradients was significantly inhibited by phosphate, arsenate and phosphonoformic acid (PFA), which are specific inhibitors of phosphate transport, but not by D-glucose. Based on these results, it is concluded that FOM transport in the small intestine is partially shared with the Na+-phosphate cotransport system and in part occurs via a H+-gradient dependent carrier-mediated system.

Original languageEnglish
Pages (from-to)292-300
Number of pages9
Journaljournal of pharmacobio-dynamics
Issue number5
Publication statusPublished - 1990
Externally publishedYes


  • Na+-cotransport
  • active transport
  • antibiotics
  • antimicrobial agent
  • brush-border membrane vesicle
  • fosfomycin
  • intestinal uptake
  • pH-dependency

ASJC Scopus subject areas

  • Pharmacology


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