The renal excretion mechanism of cefixime, a newly developed and p.o. effective cephalosporin antibiotic, was investigated by using the renal brush-border membrane vesicles from the rat kidney cortex. The initial uptake rate of cefixime into an osmotically sensitive vesicular space showed concentration and temperature dependencies, indicating the presence of a carrier-mediated transport mechanism for cefixime. Kinetic parameters for apparently saturable and nonsaturable components were evaluated as follows: maximum uptake rate was 7.32 +/- 1.07 nmol/30 sec/mg of protein; Michaelis constant was 7.35 +/- 2.04 mM; and the first-order rate constant was 0.34 +/- 0.02 nmol/30 sec/mg of protein per mM. The uptake was not affected by an inward-directed gradient of Na+, K+, Li+, Rb+ or H+. In contrast, the initial uptake rate was enhanced by an inside-positive membrane potential imposed by valinomycin. Although amino acids, dipeptides and organic cations had no effects on the uptake of cefixime, organic anions such as probenecid and p-aminohippuric acid and anion transport inhibitors such as 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid and furosemide reduced the uptake significantly. Twenty beta-lactam antibiotics including both zwitter-ionic and anionic derivatives inhibited significantly the uptake of cefixime. Furthermore, by adding probenecid in the extravesicular medium, an efflux of cefixime from the brush-border membrane vesicles was enhanced significantly at the initial stage. Benzylpenicillin, cephalothin and cephradine also enhanced an efflux of cefixime to the same extent as observed by the addition of probenecid.(ABSTRACT TRUNCATED AT 250 WORDS)