title: Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid.
abstract: OBJECTIVE
  To investigate whether drug concentrations of venlafaxine and its metabolite O-desmethylvenlafaxine in plasma can be considered as a surrogate marker of concentrations in brain/cerebrospinal fluid (CSF).
  
  
  METHODS
  For therapeutic drug monitoring purposes, plasma and CSF concentrations of venlafaxine and O-desmethylvenlafaxine were measured between November 2011 and August 2013 in 16 depressive inpatients (ICD-10 diagnoses) who were treated with daily doses of venlafaxine extended release (dose range, 75-225 mg). Daily doses were correlated with plasma and CSF levels. The correlation between venlafaxine, O-desmethylvenlafaxine, and the active moiety (AM) in plasma and CSF was calculated.
  
  
  RESULTS
  Venlafaxine in plasma (P = .005) and CSF (P = .023) correlated significantly with the daily dose, while O-desmethylvenlafaxine and the active moiety (AM = venlafaxine + O-desmethylvenlafaxine) did not. The correlation between venlafaxine, O-desmethylvenlafaxine, and the AM in plasma and CSF was highly significant (P < .001). The calculated CSF/plasma ratio was 0.74 for venlafaxine, 0.88 for O-desmethylvenlafaxine, and 0.84 for the AM.
  
  
  CONCLUSIONS
  Venlafaxine and O-desmethylvenlafaxine were found to penetrate well into CSF in patients, which indicated good availability of the drug in the brain, although the findings on CSF concentrations do not allow calculation of concentrations at the target structure within the brain. CSF/plasma ratios for venlafaxine and its metabolite were high probably due to low plasma protein binding. The poor correlation of dose to concentrations in body fluids and the highly significant correlation of plasma to CSF concentrations indicate that plasma concentration is a much better marker of drug concentration in brain than the dose.
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr 30, 52074 Aachen, Germany mpaulzen@ukaachen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
authors.forename: Sarah
authors.initials: S
authors.lastname: Groppe
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.forename: Tanja
authors.initials: T
authors.lastname: Veselinovic
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000097:blood* / Q000134:cerebrospinal fluid*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy; D000069468:Desvenlafaxine Succinate; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D000069470:Venlafaxine Hydrochloride; D000069468:Desvenlafaxine Succinate