Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a Streptococcus pneumoniae meningitis model

Using microdialysis in a rabbit model of Streptococcus pneumoniae meningitis, the pharmacokinetics and pharmacodynamics of a new fluoroquinolone, A-80556, were determined. A-80556 (10 mg/kg iv) was administered to four rabbits. Saline was given to four separate control animals. A microdialysis probe...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1996-12, Vol.38 (6), p.977-985
Main Authors: Destache, Christopher J., Pakiz, Catherine B., Stoysich, Anne M.
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacokinetics
Anti-Infective Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Disease Models, Animal
Fluoroquinolones
Medical sciences
Meningitis, Bacterial - cerebrospinal fluid
Meningitis, Bacterial - drug therapy
Meningitis, Bacterial - metabolism
Microbial Sensitivity Tests
Microdialysis
Pharmacology. Drug treatments
Pneumococcal Infections
Quinolones - pharmacokinetics
Quinolones - pharmacology
Rabbits
Streptococcus pneumoniae - drug effects
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Summary:Using microdialysis in a rabbit model of Streptococcus pneumoniae meningitis, the pharmacokinetics and pharmacodynamics of a new fluoroquinolone, A-80556, were determined. A-80556 (10 mg/kg iv) was administered to four rabbits. Saline was given to four separate control animals. A microdialysis probe perfused the CSF (2 μL/min) and effluent was collected at 0–0.25, 0.25–1, 1–2, 2–4, and 4–6 h after injection of A-80556. Seven blood samples were collected and analyzed by HPLC. At 0, 2, 4, and 6h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC0–∞.K 2.40 ± 0.272 μg.h/mL; T½β 1.07 ± 0.011 h; Vd 6.35 ± 0.50 L/kg; and Cl 4.23 ± 0.48 L/h.kg. Penetration into the CSF was 18.21%. Pharmacodynamics using time-kill curves showed a 3-log reduction in bacterial counts in CSF at 2 h after administration continuing for the remaining four hours of the experiment. These results demonstrate that microdialysis can be used for determination of drug penetration and efficacy in experimental S;. pneumoniae meningitis.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/38.6.977