Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an experimental rabbit meningitis model

Christopher J. Destache, Catherine B. Pakiz, Chris Larsen, Heather Owens, Alekha K. Dash

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

This study was designed to investigate the penetration across the blood-brain barrier of three doses of levofloxacin using a microdialysis probe implanted into the cerebrospinal fluid (CSF) of a rabbit pneumococcal meningitis model. The microdialysis guide cannula was implanted into rabbit subarachnoid space using a stereotaxic frame. After 3 days, 10 4 cfu Streptococcus pneumoniae serotype 3 in 0.3 mL saline was injected via intracisternal puncture and animals were allowed to incubate the organisms for 16-18 h. Groups of animals (n=5) then received 7, 10.5 or 14 mg/kg iv of the drug over 10 min. Plasma samples were obtained via an ear vein 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h after the antibiotic infusion. CSF microdialysis effluent samples were collected every 0.5 h for the entire experiment. Plasma and microdialysis effluent samples were analysed by HPLC. AUC 0-8 in plasma and CSF were computed using the trapezoid rule. The elimination half-life in plasma and CSF was calculated using non-linear regression analysis. The unbound peak plasma concentrations for the three doses studied were 3.9, 6.4 and 10.3 mg/L, respectively. There was a significant increase in the plasma AUC 0-8 [29.7 ± 6.3, 49.1 ± 19.1 and 67.6 ± 8.9 mg·h/L (PCSF(0-8) was significantly higher as the dose was increased (7 mg/kg, 15.8 ± 6.6; 10.5 mg/kg, 37.3 ± 7.8; and 14 mg/kg, 46.4 ± 20.9 mg·h/L; P

Original languageEnglish
Pages (from-to)611-615
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume47
Issue number5
StatePublished - 2001

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Levofloxacin
Meningitis
Cerebrospinal Fluid
Pharmacokinetics
Microdialysis
Rabbits
Area Under Curve
Pneumococcal Meningitis
Subarachnoid Space
Streptococcus pneumoniae
Blood-Brain Barrier
Punctures
Ear
Half-Life
Veins
High Pressure Liquid Chromatography
Regression Analysis
Anti-Bacterial Agents
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology

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Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an experimental rabbit meningitis model. / Destache, Christopher J.; Pakiz, Catherine B.; Larsen, Chris; Owens, Heather; Dash, Alekha K.

In: Journal of Antimicrobial Chemotherapy, Vol. 47, No. 5, 2001, p. 611-615.

Research output: Contribution to journalArticle

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