title: Oral absorption of cephalosporin antibiotics. 1. Synthesis, biological properties, and oral bioavailability of 7-(arylacetamido)-3-chloro cephalosporins in animals.
abstract: A number of 7-(arylacetamido)-3-substituted cephalosporins were prepared and tested in animals for oral absorbability. Bioavailability in mice, rats, dogs, and monkeys was determined after oral or parenteral administration. Oral bioavailability of five compounds selected for more intensive study was generally higher than that of penicillin V in all species tested. The results of ED50 testing against experimental infections in mice generally supported the bioavailability studies. Antibiotic activities were evaluated against Gram-positive and Gram-negative organisms with some derivatives expressing in vitro activity similar to cefaclor. The plasma half-life in rats was relatively short and the plasma curves were strongly influenced by probenecid, indicating rapid renal secretion. Some 7-(arylacetamido)-3-chloro cephalosporins are orally absorbed in animals to a greater extent than penicillin V, and antibacterial agent of proven clinical utility.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
authors.forename: S
authors.initials: S
authors.lastname: Kukolja
authors.forename: W E
authors.initials: WE
authors.lastname: Wright
authors.forename: J F
authors.initials: JF
authors.lastname: Quay
authors.forename: J
authors.initials: J
authors.lastname: Pfeil-Doyle
authors.forename: S E
authors.initials: SE
authors.lastname: Draheim
authors.forename: J A
authors.initials: JA
authors.lastname: Eudaly
authors.forename: R J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: Ott
authors.forename: F T
authors.initials: FT
authors.lastname: Counter
authors.forename: R D
authors.initials: RD
authors.lastname: Cooper
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002511:Cephalosporins / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004285:Dogs; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002511:Cephalosporins