title: Lung as reservoir for antidepressants in pharmacokinetic drug interactions.
abstract: BACKGROUND
  Although high-affinity imipramine binding sites have been reported in both rat and human lung, the role of the lungs in the pharmacokinetics of antidepressants has not received much attention. Substantial accumulation of selective serotonin-reuptake inhibitors (SSRIs) in the lungs has been reported. We have investigated the role of the lungs in pharmacokinetic drug interactions between tricyclic antidepressants and SSRIs.
  
  
  METHODS
  We used a carbon-11-labelled form of the imipramine derivative cyanoimipramine to measure uptake in the lungs and brain of healthy volunteers by positron emission tomography. Clomipramine (50 mg) was administered to measure the effect of antidepressants with high affinity for the serotonin transporter on lung and brain uptake.
  
  
  RESULTS
  A large proportion of the injected 11C-cyanoimipramine (68-86% in the four volunteers) was extracted by the lungs. Clomipramine decreased the lung uptake from 68% to 35% and from 81% to 54% in the two volunteers studied. By contrast, whole-brain uptake was low in control studies (1.7-2.0% in three volunteers) and increased after clomipramine administration (to 4.5-4.9%). Plasma radioactivity was also higher after clomipramine than in control studies.
  
  
  CONCLUSIONS
  The lungs may function as a reservoir for antidepressants with high affinity to the serotonin transporter. The accumulated antidepressants may be displaced by other antidepressants, and this displacement would substantially increase plasma concentrations and thus cause toxic effects.
authors.affiliation: Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan. suhara@nirs.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Suhara
authors.forename: Y
authors.initials: Y
authors.lastname: Sudo
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Okubo
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Obata
authors.forename: K
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002997:Clomipramine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002250:Carbon Radioisotopes; D002997:Clomipramine; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors