Distribution pattern of mirtazapine and normirtazapine in blood and CSF
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- 作者：Michael Paulzen ; Gerhard Gründer ; Simone C. Tauber ; Tanja Veselinovic…
- 关键词：Tetracyclic antidepressant ; Mirtazapine ; Cerebrospinal fluid ; Therapeutic drug monitoring ; NaSSA ; Blood ; brain barrier ; Blood ; cerebrospinal fluid barrier ; CSF ; BCSFB
- 刊名：Psychopharmacology
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：232
- 期：4
- 页码：807-813
- 全文大小：257 KB
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文摘
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 7.5-0?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--.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--.060). The correlation between mirtazapine and normirtazapine in serum and CSF was highly significant (r--0.664, p--.005 and r--0.885, p--.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--.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-.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.