title: Pharmacokinetic interaction between fluoxetine and omeprazole in healthy male volunteers: a prospective pilot study.
abstract: BACKGROUND
  Fluoxetine is an inhibitor of the main metabolizing enzymes (cytochrome P450 [CYP] 2C19 and CYP3A4) of omeprazole and thus might influence that drug's pharmacokinetics. The changes in omeprazole's pharmacokinetics may have clinical significance concerning efficacy and tolerability of the treatment.
  
  
  OBJECTIVE
  The aim of this study was to assess the pharmacokinetic interaction of fluoxetine with omeprazole in healthy volunteers.
  
  
  METHODS
  The study enrolled healthy adult men and consisted of 2 periods. In the first period, all subjects received a single 40-mg dose of omeprazole. This was followed by an 8-day period during which fluoxetine monotherapy (60 mg/d) was administered as a single oral daily dose. At the end of those 8 days, the subjects were administered a 40-mg dose of omeprazole with a 60-mg dose of fluoxetine. Plasma concentrations of omeprazole were determined at 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, and 12 hour(s) after study drug administration. Omeprazole plasma concentrations were determined by a validated HPLC method. Pharmacokinetic parameters of omep-razole were calculated using noncompartmental analysis. Adverse events were assessed throughout the study duration.
  
  
  RESULTS
  Eighteen healthy male volunteers (mean [SD] age, 22.11 [2.52] years [range, 18-26 years]; body mass index, 23.34 [2.31] kg/m(2) [range, 19.1-27.1 kg/m(2)]) were enrolled and completed the study. In the 2 periods of treatment, the mean Cmax of omeprazole was 730.8 ng/mL (omeprazole monotherapy) and 1725.5 ng/mL (combination treatment with fluoxetine). The observed AUC0-∞ was 1453.3 and 5072.5 ng/mL/h and AUC0-t was 1465.0 and 5185.3 ng/mL/h, respectively. The Tmax was 1.30 and 1.63 hours and the elimination rate constant was 0.753 and 0.482 hr(-1). The t½ was 0.96 and 1.47 hours, whereas the mean residence time was 2.33 and 3.35 hours, respectively. Statistically significant differences were observed for all parameters between periods 1 and 2 (all, P < 0.001).
  
  
  CONCLUSIONS
  The data found in this prospective pilot study suggest a pharmacokinetic interaction between fluoxetine and omeprazole in these healthy volunteers, but its relevance has to be confirmed.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania.
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Neag
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania.
authors.forename: Adina
authors.initials: A
authors.lastname: Popa
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Muntean
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania.
authors.forename: Sorin E
authors.initials: SE
authors.lastname: Leucuta
keywords: drug interaction; fluoxetine; omeprazole; pharmacokinetics