Cis- and trans-isomers of doxepin and desmethyldoxepin in the plasma of depressed patients treated with doxepin.

Plasma levels of doxepin and desmethyldoxepin were measured in split samples of 20 depressed patients treated with doxepin by using a conventional extraction and gas chromatography method on a packed column (method 1) and derivation of secondary amine and gas chromatography on a capillary column, allowing the separation and simultaneous quantitation of the cis- and trans-isomers of the two compounds (method 2). We have found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2. We concluded that the plasma levels of doxepin reported in most previous studies were underestimated since the cis- and trans-isomers were not separated and included in the total drug concentration. Because the activity of the two isomers is different and their proportion varies in individual patients, we suggest that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and the trans-isomers of doxepin and desmethyldoxepin be determined.