Summary
Commercial preparations of the tricyclic antidepressant doxepin contain 15% of the more active cisdoxepin and 85% of the trans-isomer. The single dose pharmacokinetics of doxepin and its major metabolite N-desmethyldoxepin were examined in 30 healthy young men.
Results for total doxepin showed wide intersubject variation in all pharmacokinetic parameters except tmax and Cmax. Plasma levels of cis-doxepin were extremely low and it was only possible to estimate the stereoselective pharmacokinetics of the parent drug in 3 subjects. The data from those particular subjects resulted in an average ratio of cis- to trans-doxepin isomers in plasma of 15:85.
In contrast, the mean plasma levels of cis-N-desmethyldoxepin in 28 subjects exceeded those of the trans-isomer at every time point after 10 h, such that the areas under the plasma concentration versus time curves (AUC) of cis-N-desmethyldoxepin were significantly higher than those of the corresponding trans-isomer. This phenomenon may play an important role in the therapeutic action of doxepin since it has been suggested that cis-N-desmethyldoxepin is pharmacologically active. In 2 subjects, however, the AUC 0-inf of trans-N-desmethyldoxepin were respectively 4 and 8 fold higher than those of the cis-isomer.
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Midha, K.K., Hubbard, J.W., McKay, G. et al. Stereoselective pharmacokinetics of doxepin isomers. Eur J Clin Pharmacol 42, 539–544 (1992). https://doi.org/10.1007/BF00314865
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DOI: https://doi.org/10.1007/BF00314865