title: Doxepin concentrations in plasma and cerebrospinal fluid.
abstract: Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF. Plasma and CSF samples were taken simultaneously from 21 patients who were treated with doxepin due to different clinical indications. The plasma concentration of both doxepin and nordoxepin correlated significantly with the oral dosage of doxepin (doxepin: r = +0.66, p < 0.001; nordoxepin: r = +0.78, p < 0.0001; Spearman's correlation). Furthermore, we found significant correlations between the plasma and CSF concentrations of both doxepin (r = +0.71; p < 0.001; Pearson's correlation) and nordoxepin (r = +0.74; p < 0.001). These highly significant correlations between the plasma and CSF concentrations indicate a constant CSF permeability of doxepin and its active metabolite nordoxepin.
authors.affiliation: Department of Neurology, University of the Saarland, Kirrberger Straße, 66421, Homburg/Saar, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schomburg
authors.forename: Daniela
authors.initials: D
authors.lastname: Remane
authors.forename: Klaus
authors.initials: K
authors.lastname: Fassbender
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
authors.forename: Jörg
authors.initials: J
authors.lastname: Spiegel
mesh_terms: D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D003866:Depressive Disorder / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D004316:Doxepin / Q000031:analogs & derivatives / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; C028701:desmethyldoxepin