Plasma levels of the cis- and trans-isomers of doxepin and desmethyldoxepin after administration of doxepin to patients.

In depressed patients treated with doxepin (Sinequan), a 15:85% mixture of cis- and trans-isomers, plasma levels of the cis- and trans-forms of doxepin and desmethyldoxepin were measured using a GLC-method with a capillary column and a nitrogen detector. A gradual increase of the concentration of the products in the plasma is seen in the first days of administration. There is a remarkable variation from patient to patient in the steady-state concentrations of trans-doxepin and of cis- and trans-desmethyldoxepin. cis-Doxepin levels are always very low. It is suggested that for studies of correlation between plasma levels and therapeutic and toxic effects of doxepin, the isomers of the parent compound and its metabolite should be measured separately.