Prediction of steady-state plasma levels of doxepin and imipramine from single dose levels in depressed outpatients.
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).
Hrdina
P D
PD
Department of Pharmacology, Faculty Medicine, University of Ottawa, Ontario, Canada.
Bakish
D
D
Swenson
S
S
Lapierre
Y D
YD
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
D004316:Doxepin; D007099:Imipramine