title: Distribution pattern of mirtazapine and normirtazapine in blood and CSF.
abstract: BACKGROUND
  The aim of this study was to investigate the distribution pattern of mirtazapine and its metabolite normirtazapine (N-desmethylmirtazapine) in blood and cerebrospinal fluid (CSF).
  
  
  OBJECTIVE
  Concentrations of mirtazapine were measured in blood serum and CSF of 16 patients treated with daily doses of 7.5-60 mg. Daily doses were correlated with serum and CSF concentrations as well as serum levels with those in CSF.
  
  
  RESULTS
  Serum levels of mirtazapine and normirtazapine showed a strong relation to the daily dose of mirtazapine of r = +0.631 and r = +0.732, respectively (p < 0.01). Between the daily doses and the CSF levels of both mirtazapine and normirtazapine, we only found a trend-wise correlation (r = +0.535, p = 0.060). The correlation between mirtazapine and normirtazapine in serum and CSF was highly significant (r = +0.664, p = 0.005 and r = +0.885, p < 0.001, respectively). High discrepancies between (total) mirtazapine levels in serum and CSF indicate a low penetration into CSF with regard to the total serum concentration as the mean of the calculated penetration ratio was 0.16 (SD = 0.11). By correcting the penetration ratio for the plasma protein binding, the mean CSF/serum ratio for the unbound fraction was 1.05 (SD 0.72, range 0.56-3.19) indicating a high passage into CSF.
  
  
  CONCLUSIONS
  Findings indicate a good ability of mirtazapine and normirtazapine to overcome the blood-cerebrospinal fluid barrier and suggest a high ability to enter the brain with sufficient drug levels at the target sites within the brain contributing to clinical efficacy.
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: Gerhard
authors.initials: G
authors.lastname: Gründer
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: Sarah E
authors.initials: SE
authors.lastname: Groppe
mesh_terms: D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid; D008875:Middle Aged; D000078785:Mirtazapine
chemical_list: D000929:Antidepressive Agents, Tricyclic; C517416:desmethylmirtazapine; D008803:Mianserin; D000078785:Mirtazapine