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

35 Scopus citations

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 (US)
Pages (from-to)611-615
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume47
Issue number5
DOIs
StatePublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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