RESUMO
Cefatrizine (SK&F 60771), a new orally-active semisynthetic cephalosporin antibiotic with broad-spectrum antibacterial activity, was compared with cephalexin and cefazolin for in vitro and in vivo antibacterial activity and pharmacokinetic behavior in laboratory animals. The average MIC values obtained with cefatrizine against gram-positive and gram-negative bacteria were superior to those obtained with cephalexin and somewhat poorer than those of cefazolin. In addition, a large percentage of the enterobacter and enterococcus isolates were found to be susceptible. Cefatrizine had a longer biological half-life and a higher peak serum level than either cefazolin or cephalexin when administered parenterally or orally to mice at 20 mg/kg. It had striking in vivo protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Hemophilus influenzae, Proteus morganii or Staphylococcus aureus reflecting its superior pharmacokinetic profile in this animal species. A variable pharmacokinetic response between animal species was observed when cefatrizine was administered either orally or parenterally to dogs, squirrel monkeys or rabbits.
Assuntos
Cefalosporinas/farmacologia , Administração Oral , Animais , Cefazolina/farmacologia , Cefalexina/farmacologia , Cefalosporinas/administração & dosagem , Cefalosporinas/metabolismo , Cães , Avaliação Pré-Clínica de Medicamentos , Escherichia coli/efeitos dos fármacos , Haplorrinos , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Triazóis/administração & dosagem , Triazóis/metabolismo , Triazóis/farmacologiaRESUMO
SK&F 59962, a new parenteral cephalosporin was found to have a high order of in vitro and in vivo antibacterial activity against a broad-spectrum of clinical isolates. When tested in vitro against gram-negative organisms, SK&F 59962 was consistently more active than cefazolin and far superior to cephalothin. This new antibiotic had activity equal to that of cephalothin against gram-positive bacteria. Enterobacter species were found to be susceptible to SK&F 59962. In mouse infection studies using bacterial pathogens, SK&F 59962 had protective activity of the order of that of cefazolin and superior to that of cephalothin. Following parenteral administration the serum profile of SK&F 59962 in the mouse, dog and squirrel monkey was similar to that of cephalothin. SK&F 59962 and cephalothin had lower peak serum concentrations and shorter biologic half-lives than those of cefazolin.
