title: Prediction of steady-state plasma levels of doxepin and imipramine from single dose levels in depressed outpatients.
abstract: We have investigated the predictive value of single dose levels for steady state levels of two commonly used antidepressants, doxepin (DOX) and imipramine (IMI) in a population of 40 outpatients with unipolar depression. After a wash-out period, patients were given 75 mg of either doxepin or imipramine and blood samples were drawn 16 h after the dose. Treatment was continued for 2 weeks on a fixed 100 mg/day dose and after that the dose was adjusted according to patients' response. Drugs and their demethylated metabolites were determined weekly using a GC technique. There was a large (more than 5-fold) inter-individual variation in both the single dose and steady-state levels of the two drugs. However, a significant correlation was found between the single-dose levels and initial steady-state levels for both. The respective linear regression equations were: DOX (parent drug & demethylated metabolite): y = 1.4x + 16.8; r = 0.75, p less than 0.001; IMI (parent drug & demethylated metabolite): y = 3.1x + 4.9; r = 0.85; p less than 0.001. These results confirm, in a population of depressed outpatients, previous findings of a significant correlation between single dose and steady state plasma levels of imipramine, and indicate for the first time that such a correlation also exists for another commonly used tricyclic antidepressant, doxepin. From this relationship, dose requirement can be estimated for individual patients to achieve a desired steady-state concentration of total tricyclics (parent drug & metabolite).
authors.affiliation: Department of Pharmacology, Faculty Medicine, University of Ottawa, Ontario, Canada.
authors.forename: P D
authors.initials: PD
authors.lastname: Hrdina
authors.forename: D
authors.initials: D
authors.lastname: Bakish
authors.forename: S
authors.initials: S
authors.lastname: Swenson
authors.forename: Y D
authors.initials: YD
authors.lastname: Lapierre
mesh_terms: D000293:Adolescent; D000328:Adult; D000553:Ambulatory Care; D003866:Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011336:Probability
chemical_list: D004316:Doxepin; D007099:Imipramine