Ishizawa T, Sadahiro S, Hosoi K, Tamai I, Terasaki T, Tsuji A
Meiji Seika Kaisha, Ltd., Pharmaceutical Research Center, Yokohama, Japan.
J Pharmacobiodyn. 1992 Sep;15(9):481-9. doi: 10.1248/bpb1978.15.481.
In order to clarify the mechanism of intestinal absorption of an antibiotic, fosfomycin (FOM), the uptakes of FOM by rabbit and human small intestinal brush-border membrane vesicles (BBMV) were studied. The initial uptake of FOM by BBMV at 15 s was saturable at a higher concentration of FOM. The kinetic parameters at 37 degrees C of the saturable uptake expressed by the Michaelis-Menten equation were Kt = 5.17 mM and Jmax = 3.88 nmol/15 s/mg protein for rabbits, and Kt = 4.03 mM and Jmax = 1.90 nmol/15 s/mg protein for humans. The most efficient uptake was observed in the presence of both inward-directed Na(+)- and H(+)-gradients in both mammals. The uptake of FOM was inhibited by inorganic phosphate, FOM glycol which is a degradation product of FOM in the gastric juice and specific inhibitors of phosphate transport such as arsenate and phosphonoacetic acid. These findings confirmed that FOM absorption from rabbit and human small intestines is associated with the phosphate transport system. These transport phenomena of FOM are in close agreement with those obtained previously in rat BBMV studies. Judging from the results obtained for three mammalian species, rat, rabbit and human, it was concluded that carrier-mediated transport via the phosphate transport system is a very important pathway of intestinal absorption of FOM.
为阐明抗生素磷霉素（FOM）的肠道吸收机制，研究了兔和人小肠刷状缘膜囊泡（BBMV）对FOM的摄取情况。在较高浓度的FOM下，BBMV在15秒时对FOM的初始摄取具有饱和性。用米氏方程表示的37℃下饱和摄取的动力学参数，兔的Kt = 5.17 mM，Jmax = 3.88 nmol/15秒/毫克蛋白质；人的Kt = 4.03 mM，Jmax = 1.90 nmol/15秒/毫克蛋白质。在两种哺乳动物中，当存在内向的Na⁺和H⁺梯度时，观察到最有效的摄取。FOM的摄取受到无机磷酸盐、FOM在胃液中的降解产物FOM二醇以及磷酸盐转运的特异性抑制剂如砷酸盐和膦酰乙酸的抑制。这些发现证实兔和人小肠对FOM的吸收与磷酸盐转运系统有关。FOM的这些转运现象与先前在大鼠BBMV研究中获得的结果密切一致。从大鼠、兔和人这三种哺乳动物获得的结果判断，得出结论：通过磷酸盐转运系统的载体介导转运是FOM肠道吸收的一个非常重要的途径。
