title: A comparison of duloxetine plasma levels in postbariatric surgery patients versus matched nonsurgical control subjects.
abstract: BACKGROUND
  Bariatric surgery such as the Roux-en-Y gastric bypass (RYGB) is currently used as a treatment for severe obesity. Alteration of the gastrointestinal tract by this procedure suggests a potential for clinically significant alterations in the bioavailability of ingested medications including antidepressants.
  
  
  OBJECTIVE
  The purpose of this trial was to determine to what extent the RYGB procedure alters the area under the plasma concentration/time curve (AUC(0-infinity)) of the antidepressant, duloxetine.
  
  
  METHODS
  Ten subjects who were 1 year post-RYGB where compared with healthy control subjects matched for body mass index, age, and sex. Ultrarapid or poor metabolizers for cytochrome P450 2D6 were excluded from the study. Subjects received a single dose of 60 mg of duloxetine. Nineteen plasma samples were obtained during 72 hours to characterize the plasma level profile.
  
  
  RESULTS
  The mean AUC(0-infinity) was significantly smaller for the postbariatric surgery (PBS) group (646.74 ng × h/mL [SD, 79.70; range, 539.57-791.62], P = 0.017) compared to the nonsurgical control group (1119.91 ng × h/mL [SD, 593.40; range, 415.5-2426.56]). The Tmax was also significantly shorter for the PBS group (2.2 hours) compared to the nonsurgical control group (6 hours; P = 0.005). No significant difference in Cmax or half-life was identified.
  
  
  CONCLUSIONS
  To our knowledge, this is the first reported study exploring duloxetine pharmacokinetics PBS. This trial found that the bariatric surgery group was exposed to only 57.7% of duloxetine as compared to the nonsurgery group. This finding suggests that clinicians need to monitor patients closely after bariatric surgery and that further exploration of the effects of bariatric surgery on antidepressant pharmacokinetic parameters is warranted.
authors.affiliation: Department of Clinical Neuroscience, University of North Dakota School of Medicine and Health Sciences, Fargo, ND 58107-1415, USA. jroerig@nrifargo.com
authors.forename: James L
authors.initials: JL
authors.lastname: Roerig
authors.forename: Kristine J
authors.initials: KJ
authors.lastname: Steffen
authors.forename: Cheryl
authors.initials: C
authors.lastname: Zimmerman
authors.forename: James E
authors.initials: JE
authors.lastname: Mitchell
authors.forename: Ross D
authors.initials: RD
authors.lastname: Crosby
authors.forename: Li
authors.initials: L
authors.lastname: Cao
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D000068736:Duloxetine Hydrochloride; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009658:North Dakota; D013876:Thiophenes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride