Doxepin inhibits CYP2D6 activity in vivo.
OBJECTIVE
Doxepin is a tricyclic antidepressant formulated as a mixture of E-(trans) and Z-(cis) stereoisomers. Cytochrome P450 2D6 (CYP2D6) catalyzes the hydroxylation of E-doxepin and E-N-desmethyldoxepin stereospecically. There is evidence that tricyclic antidepressants might inhibit CYP2D6 activity but there is no data about the influence of doxepin on CYP2D6.


METHODS
Eleven patients diagnosed with depression according to ICD-10 criteria were included in the study. After wash-out period, before doxepin treatment, sparteine metabolic ratio (MR1) was assessed. After 2-weeks of doxepin treatment, MR2 was estimated. Sparteine and its metabolites were determined in urine by gas chromatographic method of Eichelbaum et al.


RESULTS
Based on MR1 values, 10 patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor metabolizer). During the study, after doxepin treatment, none of patients has changed phenotype status. However, MR2 values were statistically significantly higher than MR1.


CONCLUSIONS
These results show the inhibitory effect of doxepin on CYP2D6 activity and may be of clinical value, especially in polymedicated patients treated with other CYP2D6 substrates or inhibitors.
Szewczuk-Bogusławska
Monika
M
Department of Psychiatry, University of Medicine, Pasteura 10, PL 50-367 Wrocław, Poland. msbog@psych.am.wroc.pl
Kiejna
Andrzej
A
Beszłej
Jan A
JA
Orzechowska-Juzwenko
Krystyna
K
Milejski
Piotr
P
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003863:Depression / Q000188:drug therapy / Q000201:enzymology; D004316:Doxepin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000929:Antidepressive Agents, Tricyclic; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004316:Doxepin; D019389:Cytochrome P-450 CYP2D6