title: The effect of sertraline on the pharmacokinetics of desipramine and imipramine.
abstract: OBJECTIVE
  To examine the pharmacokinetic interaction between the selective serotonin reuptake inhibitor sertraline and the tricyclic antidepressants desipramine or imipramine in 12 healthy male subjects.
  
  
  METHODS
  Participants received a 50 mg single dose of either desipramine or imipramine under three conditions: alone, after a single 150 mg dose of sertraline, and after the eighth daily 150 mg dose of sertraline. Plasma samples were analyzed for desipramine or imipramine concentration by HPLC with electrochemical detection, and pharmacokinetics were determined with use of noncompartmental analysis of individual data.
  
  
  RESULTS
  Multiple-dose, but not single-dose, treatment with sertraline significantly reduced apparent plasma clearance (CL/F) and prolonged the half-life of desipramine relative to baseline. These changes resulted in higher plasma desipramine concentrations, as indicated by a significant increase in maximum plasma concentration (Cmax) and area under the plasma concentration-time curve extrapolated to infinity [AUC(0-infinity)] (22% and 54%, respectively). Both single- and multiple-dose treatment with sertraline significantly reduced the CL/F of imipramine. This effect was stronger after multiple predoses of sertraline, when imipramine Cmax and AUC(0-infinity) were increased by 39% and 68%, respectively. These treatment effects were consistent between individuals.
  
  
  CONCLUSIONS
  This pharmacokinetic interaction is likely the result of an inhibition of CYP2D6 tricyclic metabolism by sertraline. When a tricyclic antidepressant, such as desipramine or imipramine, is coadministered with sertraline, lower dosages of the tricyclic agents may be necessary to prevent elevated tricyclic levels.
authors.affiliation: Eli Lilly and Company, Lilly Laboratory for Clinical Research, Indianapolis, IN 46202, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kurtz
authors.forename: R F
authors.initials: RF
authors.lastname: Bergstrom
authors.forename: M J
authors.initials: MJ
authors.lastname: Goldberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Cerimele
mesh_terms: D015057:1-Naphthylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003891:Desipramine / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020280:Sertraline
chemical_list: D015057:1-Naphthylamine; D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline