DISTRIBUTION AND METABOLISM OF DOXEPIN

Drug metabolism studies with doxepin in rats and dogs reflect the fundamental similarity of its structure to that of the related tricyclic psychotherapeutic agents, amitriptyline and imipramine. Doxepin is well absorbed after oral administration and measurable amounts of doxepin and demethyl doxepin quickly appear in the blood. Although numerous metabolites of doxepin are observed in liver and in urine, only doxepin and demethyl doxepin are found in the rat brain, where the same ratio of cis- and trans-isomers as in the administered drug is still present. Metabolic transformations include demethylation, N-oxidation, hydroxylation and glucuronide formation. In the rat, doxepin and its metabolites are found in all tissues examined but, with the exception of the pigmented eye, are rapidly cleared. This affinity for melanin is also reflected in studies in vitro with beef eyeball melanin, where, however, doxepin is less strongly bound than is amitriptyline. © 1969.