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

Christopher J. Destache, Catherine B. Pakiz, Anne M. Stoysich

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 At 0, 2, 4, and 6 h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC(0-∞), 2.40 ± 0.272 μg.h/mL; T( 1/4 β) 1.07 ± 0.011 h; V(d) 6.35 ± 0.50 L/kg; and Cl(t), 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.

Original languageEnglish
Pages (from-to)977-985
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume38
Issue number6
DOIs
StatePublished - Dec 1996

Fingerprint

A 80556
Pneumococcal Meningitis
Microdialysis
Pharmacokinetics
Granulocyte-Macrophage Colony-Stimulating Factor
Rabbits
Bacterial Load
Fluoroquinolones
Area Under Curve
High Pressure Liquid Chromatography
Injections
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology

Cite this

Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a Streptococcus pneumoniae meningitis model. / Destache, Christopher J.; Pakiz, Catherine B.; Stoysich, Anne M.

In: Journal of Antimicrobial Chemotherapy, Vol. 38, No. 6, 12.1996, p. 977-985.

Research output: Contribution to journalArticle

@article{2ceeb3215ebc4786b9d98cad10b98836,
title = "Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a Streptococcus pneumoniae meningitis model",
abstract = "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 6 h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC(0-∞), 2.40 ± 0.272 μg.h/mL; T( 1/4 β) 1.07 ± 0.011 h; V(d) 6.35 ± 0.50 L/kg; and Cl(t), 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.",
author = "Destache, {Christopher J.} and Pakiz, {Catherine B.} and Stoysich, {Anne M.}",
year = "1996",
month = "12",
doi = "10.1093/jac/38.6.977",
language = "English",
volume = "38",
pages = "977--985",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Pharmacodynamics and pharmacokinetics of A-80556 using microdialysis in a Streptococcus pneumoniae meningitis model

AU - Destache, Christopher J.

AU - Pakiz, Catherine B.

AU - Stoysich, Anne M.

PY - 1996/12

Y1 - 1996/12

N2 - 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 6 h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC(0-∞), 2.40 ± 0.272 μg.h/mL; T( 1/4 β) 1.07 ± 0.011 h; V(d) 6.35 ± 0.50 L/kg; and Cl(t), 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.

AB - 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 6 h 300 μL of CSF was withdrawn for pharmacodynamic measurements. Plasma A-80556 concentrations demonstrated AUC(0-∞), 2.40 ± 0.272 μg.h/mL; T( 1/4 β) 1.07 ± 0.011 h; V(d) 6.35 ± 0.50 L/kg; and Cl(t), 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.

UR - http://www.scopus.com/inward/record.url?scp=0030451596&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030451596&partnerID=8YFLogxK

U2 - 10.1093/jac/38.6.977

DO - 10.1093/jac/38.6.977

M3 - Article

VL - 38

SP - 977

EP - 985

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 6

ER -