title: Duloxetine enters the brain - But why is it not found in the cerebrospinal fluid.
abstract: BACKGROUND
  Antidepressants enter the brain to reach their site of action in a different extent. However, there has been no study to date about duloxetine's ability to enter the brain and cerebrospinal fluid. Aim of this study was to measure blood and cerebrospinal fluid concentrations of duloxetine and to account for the distribution between the two compartments.
  
  
  METHODS
  Concentrations of duloxetine were measured in blood serum and cerebrospinal fluid of 19 patients treated with daily doses of 30-120mg. Daily doses were correlated with serum and cerebrospinal fluid concentrations and serum concentrations were correlated with concentrations in cerebrospinal fluid.
  
  
  RESULTS
  Serum concentrations of duloxetine showed a moderate but significant correlation with the applied daily dose, r=+0.473, p=0.04. Duloxetine concentrations in the cerebrospinal fluid above the designated limit of quantification of 2.0ng/mL were only found in three of the 19 patients.
  
  
  CONCLUSIONS
  Contrasting to own preceding studies on venlafaxine, mirtazapine and citalopram with comparably high concentrations in cerebrospinal fluid, the here presented findings indicate that duloxetine shows a very different distribution pattern. Very low concentrations in the cerebrospinal fluid may be due to the fact that the drug crosses the blood-cerebrospinal fluid barrier much worse than other antidepressants do, suggesting a low ability of duloxetine to enter the brain. Alternatively, low drug concentrations may be interpreted in a sense of a missing residence time in cerebrospinal fluid due to active transport mechanisms out of this environment either back into the bloodstream or into the brain.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA - Translational Brain Medicine. Electronic address: mpaulzen@ukaachen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA - Translational Brain Medicine.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA - Translational Brain Medicine.
authors.forename: Tanja
authors.initials: T
authors.lastname: Veselinovic
authors.affiliation: Medical Care Center, Dr. Stein and Colleagues, Moenchengladbach, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA - Translational Brain Medicine.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lammertz
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride
keywords: BCSFB; Blood–brain barrier; Blood–cerebrospinal fluid barrier; CSF; Cerebrospinal fluid; Duloxetine; Therapeutic drug monitoring