IN VITRO AND IN VIVO LABORATORY STUDIES ON THREE HYDROXYIMINOPHENYLACETYL CEPHALOSPORINS WITH PARTICULAR REFERENCE TO SK&F 80303, AN UNUSUALLY LONG-ACTING CEPHALOSPORIN

• Published in: Journal of antibiotics Vol. 32; no. 11; pp. 1161 - 1167
• Main Authors: URI, JOSEPH V., ACTOR, PAUL, ZAJAC, IHOR, PITKIN, DONALD H., PHILLIPS, LILLIAN, GUARINI, JOSEPH R., BARTUS, HENRY F., POLANSKY, THEODORE J., DUNN, GEORGE L., HOOVER, JOHN R. E., WEISBACH, JERRY A.
• Format: Journal Article
• Language: English
• Published: Japan JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1979
• Subjects: Animals; Bacteria - drug effects; Bacteria - enzymology; Blood Proteins - metabolism; Cefazolin - pharmacology; Cephalosporinase - metabolism; Cephalosporins - metabolism; Cephalosporins - pharmacology; Haplorhini; Kinetics; Male; Mice; Microbial Sensitivity Tests; Protein Binding; Rabbits; Time Factors
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.32.1161

Three cephalosporins with 7-(2-hydroxyiminophenylacetamido) side chains (SK&F 79433, 80000 and 80303), differing in their 3-substituents, exhibited similar broad-spectrum antibacterial activity in vitro against strains of Staphylococcus aureus, Streptococcus faecalis and various Gram-negative bacilli. All three were active in vivo (s.c., mouse) against S. aureus, Esclrerichia coli or Klebsiella pnemnoniae, but they differed significantly in serum pharmacokinetic profiles. SK&F 80303 produced high and extremely prolonged serum levels and protected mice when administered up to 24 hours prior to challenge with β-lactamase-producing S. aureus or K. pneumoniae NS. It was resistant to hydrolysis by β-lactamases from S. aureus, and variably so to β-lactamases from E. coli strains. SK&F 80303 was bacteriolytic to logarithmically growing S. aureus, E. coli, Proteus mirabilis, K. pneumoniae and Enterobacter cloacae (partially).SK&F 80303 illustrates further the effect of the 3-sulfoalkyltetrazole substituent on the pharmacokinetic properties of cephalosporins. Its combined biological properties make it a possible candidate for therapeutic and long-term prophylactic use.