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Psychopharmacology

Distribution pattern of mirtazapine and normirtazapine in blood and CSF.


PMID 25150039

Abstract

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). 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. 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. 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.