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-tetr azol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid] and cefotaxime [7 beta-[2-(2-aminothiazol-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 subcutaneously to mice and intramuscularly to rats, rabbits and dogs. The cefmenoxime and cefotaxime levels in plasma and tissues reached a peak in 15 approximately 30 minutes after administration. The cefmenoxime levels in plasma were slightly higher than that of cefmenoxime in rats and slightly lower in mice, rabbits and dogs. The tissue levels of cefmenoxime, however, 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.