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Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration

Denis Frasca1, Claire Dahyot-Fizelier, Christophe Adier

  • 1Inserm U1070, Pole Biologie Santé, Poitiers, France.

Antimicrobial Agents and Chemotherapy
|November 27, 2013
PubMed

Insights

Metronidazole distributes well into cerebrospinal fluid (CSF) in brain-injured patients, reaching 86% of unbound plasma levels. Its metabolite, hydroxymetronidazole, also distributes into CSF but at lower concentrations.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Clinical Pharmacy

Background:

  • Metronidazole is an antibiotic used for anaerobic infections.
  • Understanding its distribution in the central nervous system is crucial for treating brain infections.

Purpose of the Study:

  • To investigate the distribution and pharmacokinetics of metronidazole and its metabolite, hydroxymetronidazole, in the cerebrospinal fluid (CSF) of brain-injured patients.

Main Methods:

  • Four brain-injured patients with external ventricular drains received metronidazole (500 mg every 8 hours).
  • CSF and plasma samples were collected over 8 hours at steady state.
  • Drug concentrations were quantified using high-performance liquid chromatography.
  • Noncompartmental pharmacokinetic analysis was performed.

Main Results:

  • Metronidazole showed extensive distribution into CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%.
  • CSF metronidazole concentrations were relatively flat compared to plasma.
  • Hydroxymetronidazole concentrations were significantly lower in both CSF and plasma.
  • The CSF to unbound plasma AUC0-τ ratio for hydroxymetronidazole was 79% ± 16%.

Conclusions:

  • Metronidazole achieves substantial concentrations in the CSF of brain-injured patients.
  • The pharmacokinetic profile of metronidazole in CSF differs from plasma, with less fluctuation.
  • Hydroxymetronidazole is present at lower levels in CSF compared to the parent drug.

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