title: L-656,575 (OCP-9-176): a novel oxacephem. Pharmacokinetics and experimental chemotherapy.
abstract: L-656,575 is a new oxacephem that, based on studies in rhesus monkeys, is expected to have a moderately long half-life in humans. After administration of a 10-mg/kg dose by the intramuscular route to rhesus monkeys, peak serum concentrations of 32-54 micrograms/ml were seen at about 30 minutes, and the half-life was estimated to be 63 minutes. Urinary recovery of administered dose was greater than 94% in 6 hours. In mice given a 20-mg/kg dose by the subcutaneous route, a peak serum concentration of 22.9 microgram/ml was observed at 15 minutes after dosing, and the half-life in serum was about 18 minutes. Urinary recovery of the dose was 59% in 6 hours. In another study in mice, administration of probenecid did not extend the half-life of L-656,575, suggesting that the antibiotic is excreted primarily by glomerular filtration in this species. Binding to human plasma proteins was 30% at drug concentrations from 25-100 micrograms/ml. L-656,575 also was shown to be efficacious in experimental bacteremias due to Gram-positive and Gram-negative pathogens in mice, thus confirming the broad spectrum of activity demonstrated for L-656,575 in vitro.
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D001798:Blood Proteins / Q000378:metabolism; D002442:Ceftazidime / Q000493:pharmacokinetics; D002511:Cephalosporins; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D051379:Mice; D011485:Protein Binding
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D002511:Cephalosporins; C057304:L 656575; D002442:Ceftazidime