The levels of cefmenoxime (SCE-1365) [7j3-[2-(2-aminothiazol-4-yl)-[Z]-2-methoxyiminoacetamido]-3-[(1-methyl-IH-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid] and cefotaxime [7/3-[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 -30 minutes 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, 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.Indole-positive Proteus, Haemophilus influenzae, Serratia marcescens, Citrobacter freundii and Enterobacter cloacae are less susceptible to commercially available cephalosporinsl,2), and recently, cephalosporin-resistant strains of Escherichia coli and Klebsiella pneumoniae are increasing3). Against these bacteria, cefmenoxime (SCE-1365) shows a more potent antibacterial activity than do cefuroxime, cefoxitin, cefmetazole, cefotiam and cefazolin, and its in vitro activity wasceph-3-em-4-carboxylic acid] against several bacterial species2>. Similar protective activities of cefinenoxime and cefotaxime were observed in mice infected intraperitoneally with many bacterial strains.However, cefmenoxime shows a more potent activity than cefotaxime does in mice infected intraperitoneally with certain strains of Proteus vulgaris and Proteus morganii and in model infections, such as respiratory tract infection induced by K. pneumoniae and urinary tract infection induced by P. mirabilis2).Therefore, it is imperative to conduct a comparative study on plasma levels, tissue distribution and urinary and biliary excretion of cefmenoxime and cefotaxime. acetamidol --3-hydroxymethyl-ceph-3-em-4-carboxylic acid] were prepared in Takeda Chemical Industries, Ltd. (Fig. 1). The sodium salt form of the cephalosporins was used in this study. A single dose of 20 mg/kg of cephalosporin dissolved in saline was administered subcutaneously to mice (2 mg/ml, 0.1 m1/10 g), and intramuscularly to rats (10 mg/kg, 0.2 ml/100 g), rabbits (20 mg/ml, 1 ml/kg), and dogs (100 mg/ml, 0.2 ml/kg). Animals Male 5-week-old Slc: ICR...
