title: Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.
abstract: This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.
authors.affiliation: Inserm U1070, Pole Biologie Santé, Poitiers, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Frasca
authors.forename: Claire
authors.initials: C
authors.lastname: Dahyot-Fizelier
authors.forename: Christophe
authors.initials: C
authors.lastname: Adier
authors.forename: Olivier
authors.initials: O
authors.lastname: Mimoz
authors.forename: Bertrand
authors.initials: B
authors.lastname: Debaene
authors.forename: William
authors.initials: W
authors.lastname: Couet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchand
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D001812:Blood-Brain Barrier / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000473:pathology; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004322:Drainage; D045604:Extracellular Fluid / Q000737:chemistry*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000378:metabolism / Q000493:pharmacokinetics*; D008875:Middle Aged
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole