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

Abstract

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 ug/ml) after parenteral administration and was approximately threefold that of cephalothin (20 pg/ml), but less than that of cephaloridine (83 ug/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.

Comparative Serum Levels and Protective Activity of Parenterally Administered Cephalosporins in Experimental Animals

“…This was reflected by the presence of a biologically active metabolite in the urine of mice treated with cephacetrile, cephapirin, or cephalothin. The serum values obtained in mice with cephalothin, cephaloridine, and cephapirin are in general agreement with those reported by other investigators (3,17). Wick and Preston have reported generally lower values for cefazolin, cephalothin, cephaloridine, and cephanone in mice (22).…”

EXPERIMENTAL PNEUMOCOCCUS INFECTION IN MICE: COMPARATIVE IN VITRO AND IN VIVO EFFECT OF CEFUROXIME, CEFOTAXIME AND CEFTRIAXONE

“…10 times the MIC, a maximal bactericidal rate is achieved (7). The killing-curves were roughly similar (0-5h) at all concentrations for all 3 (10,20). cephalosporins.…”

“…The difference in effect in vivo in spite of similar MICs for the three cephalosporins could be due to various factors concerning antibiotic activity in vitro or in vivo, such as early bactericidal activity (2,16,20), post-antibiotic effect (12,27), protein binding (1,5,18), or pharmacokinetic properties The determination of the MIC or MBC does not reveal the early bactericidal potential of the antibiotic. For this purpose, time-kill curves are necessary (16).…”

Pharmacokinetics and Clinical Use of Cephalosporin Antibiotics

“…Metabolism and Excretion-A study in mice and dogs using paper chromatographic techniques showed that no metabolites of cephradine could be found in the urine (71,73). A study in humans also could not find any metabolites of cephradine (63).…”