Multiple-dose doxepin kinetics in depressed patients

Abstract

Doxepin (DOX) and desmethyldoxepin (DMD) kinetics were examined in seven depressed patients receiving single daily doses of 150 mg DOX for 1 to 3 wk. Blood samples were collected at 0, 4, 12, 15, 18, and 24 hr after the first dose, at bedtime before doses 7, 14, and 21, and at 4, 12, 15, 18, and 24 hr after the last dose. Plasma concentrations of DOX and DMD were analyzed by high-pressure liquid chromatography. Clinical response to DOX treatment was evaluated by the Zung self-rating depression scale and the Hamilton rating scale for depression. Mean DOX t1/2 after the first dose was 17.7 hr, and it rose to 21.8 hr after the last dose. Mean DMD t1/2 was not significantly affected by multiple dosing (34.2 hr after first dose and 37.1 hr after last dose). Mean values for plasma clearance, volume of distribution, and first-pass metabolism were 0.87 l/hr/kg, 23.8 l/kg, and 69.5%. In depressed patients kinetics were in the normal range. Steady-state concentrations of DOX and DMD were reached within 2 wk of beginning DOX dosing. The concentration-response curve indicated strong correlation between total DOX concentration (DOX + DMD) and antidepressant effect (r2 = 0.76).