Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed patients

被引:0
|
作者
Michael Deuschle
Sebastian Härtter
Christoph Hiemke
Harald Standhardt
Isabella Heuser
机构
[1] Max Planck Institute of Psychiatry,
[2] Clinical Institute,undefined
[3] Kraepelinstrasse 10,undefined
[4] D-80804 München,undefined
[5] Germany,undefined
[6] University of Mainz,undefined
[7] Department of Psychiatry,undefined
[8] Untere Zahlbacher Strasse 8,undefined
[9] D-55131 Mainz,undefined
[10] Germany,undefined
[11] M. Deuschle (♪),undefined
[12] Central Institute of Mental Health,undefined
[13] J 5,undefined
[14] D-68159 Mannheim,undefined
[15] Germany,undefined
来源
Psychopharmacology | 1997年 / 131卷
关键词
Key words Doxepin; CSF; Plasma; Doxepin metabolites;
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学科分类号
摘要
Little information exists on the concentrations of antidepressants and their metabolites in CSF. We measured plasma and CSF levels of trans-doxepin (trans-DOX) and DOX metabolites in 12 depressed patients treated with DOX (250 mg/day) for 6 days. Spinal taps and blood samples were taken on day 7, 10 h after drug administration. Trans-DOX, cis-desmethyldoxepin (cis-DM-DOX), trans-desmethyldoxepin (trans-DM-DOX) and di-desmethyldoxepin (DDM-DOX) were analyzed in CSF and plasma samples by HPLC with column-switching. Although DOX was given as a mixture of 85% trans-DOX and 15% of the pharmacologically more active cis-DOX, we found similar amounts of cis-DM-DOX and trans-DM-DOX in plasma (59.8 ± 45.1 versus 72.0 ± 60.0 ng/ml; NS), suggesting that isomerization of DOX had taken place. Trans-DOX and DOX metabolites could be detected in CSF of most patients. Relatively low CSF concentrations of the active metabolite cis-DM-DOX were measured. Clinical efficacy, as assessed by HAMD scores, was not significantly related to plasma or CSF concentrations of trans-DOX or its metabolites. Trans-DOX and DOX metabolites were distributed differently between plasma and CSF. It is concluded that isomerization of DOX is not only relevant for neuronal uptake inhibition, but also for the transport of the metabolites.
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页码:19 / 22
页数:3
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