Absorption, distribution and excretion of Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin, in mice, rats, rabbits and dogs.

Abstract

The levels of cefmenoxime (SCE-1365) [7.beta.-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid] and cefotaxime [7.beta.-[2-(2-aminoehiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-acetoxymethyl-ceph-3-em-4-carboxylic acid] in plasma and tissues and the excretion in urine and bile of experimental animals were compared. A single dose of 20 mg/kg of cephalosporins was administered s.c. to mice and i.m. to rats, rabbits and dogs. The cefmenoxine and cefotaxime levels in plasma and tissues reached a peak 15-30 min after administration. The cefmenoxime levels in plasma were slightly higher than that of cefotaxime in rats and slightly lower in mice, rabbits and dogs. The tissue levels of cefmenoxime were much higher than those of cefotaxime. In mice and rats, cefmenoxime was distributed in high concentration to various tissues in the descending order of the kidney, plasma, liver, lung, spleen and brain; in rabbits, kidney, plasma, lung, liver, spleen and brain; and in dogs, kidney, liver, plasma, lung, spleen and brain. The plasma and tissue levels of cefmenoxime persisted much longer than those of cefotaxime. Both cephalosporins were excreted principally in the urine. A high biliary excretion of cefmenoxime was observed in rats and dogs. In the specimens from animals given cefotaxime, deacetylcefotaxime was found in various amounts.