Comparison of the Chemotherapeutic and Pharmacodynamic Activities of Cephradine, Cephalothin, and Cephaloridine in Mice

摘要

Cephradine, a new semisynthetic cephalosporin derivative, is 7[d(−)-2-amino-2-(1,4-cyclohexadien-1-yl) acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate. The compound has a broad spectrum of antimicrobial activity in vitro. When given subcutaneously to mice, cephradine was appreciably more effective than cephalothin against infections induced by penicillinase-producing Staphylococcus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae strains. Cephradine and cephaloridine possessed equivalent activity in treating infections caused by these same three gram-negative bacteria. The mean total bioactivity of cephradine in the serum of mice peaked within 30 min (59 μg/ml) after parenteral administration and was approximately threefold that of cephalothin (20 μg/ml), but less than that of cephaloridine (83 μg/ml). Nearly all of the administered cephradine (84%) and cephaloridine (70%) were excreted in the urine as the parent compounds. In contrast, only 47% (total bioactivity) of administered cephalothin was recovered, an amount that represented only 15 to 20% of the parent substance.