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- Title
Distribution pattern of mirtazapine and normirtazapine in blood and CSF.
- Authors
Paulzen, Michael; Gründer, Gerhard; Tauber, Simone; Veselinovic, Tanja; Hiemke, Christoph; Groppe, Sarah
- Abstract
Rationale: 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). Objectives and methods: 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.
- Subjects
MIRTAZAPINE; BLOOD testing; CEREBROSPINAL fluid; DRUG metabolism; DRUG dosage; BLOOD serum analysis
- Publication
Psychopharmacology, 2015, Vol 232, Issue 4, p807
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-014-3717-9