title: The pharmacodynamic effect of amoxycillin and danofloxacin against Actinobacillus pleuropneumoniae in an in-vitro pharmacodynamic model.
abstract: The pharmacodynamic effect of amoxycillin and danofloxacin against two strains of Actinobacillus pleuropneumoniae was evaluated in an in-vitro pharmacodynamic model. For amoxycillin peak concentrations of 0.5, 1, and 4 microg ml(-1)and half-lives of 3 and 15 hours were examined. For danofloxacin peak concentrations of 0.125, 0.5, and 1. 5 microg ml(-1)and half-lives of 1.5 and 7 hours were evaluated. The initial bactericidal effect was measured as the reduction in colony count (log CFU ml(-1)) during the first three hours, and the overall pharmacodynamic effect as the area under the bacterial growth versus time curve (AUBC). The initial bactericidal effect of amoxycillin was maximal at peak concentrations of two to four times the MIC. Peak concentration and half-life only influenced the pharmacodynamic effect of amoxycillin if the antibiotic concentration fell below the MIC during the experiments, which is consistent with time >MIC as the most important parameter of pharmacodynamic effect of beta-lactam drugs. For danofloxacin maximal bactericidal effect initially was observed at peak concentrations of at least eight times the MIC. The pharmacodynamic effect was dependent on the peak concentration. The half-life only influenced the pharmacodynamic effect of danofloxacin in experiments with a peak concentration MIC ratio of less than eight. This indicated that for danofloxacin the peak concentration was the major determinant of pharmacodynamic effect.
authors.affiliation: Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
authors.forename: R H
authors.initials: RH
authors.lastname: Lindecrona
authors.forename: C
authors.initials: C
authors.lastname: Friis
authors.forename: N E
authors.initials: NE
authors.lastname: Jensen
mesh_terms: D016977:Actinobacillus pleuropneumoniae / Q000187:drug effects*; D000658:Amoxicillin / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024841:Fluoroquinolones; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D010406:Penicillins / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010406:Penicillins; C068581:danofloxacin; D000658:Amoxicillin