title: The influence of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite.
abstract: OBJECTIVE
  To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of atomoxetine and paroxetine in healthy volunteers.
  
  
  METHODS
  22 healthy volunteers, extensive metabolizers, took part in this open-label, non-randomized, clinical trial. The study consisted of two periods: Reference, when a single oral dose of 25 mg atomoxetine was administrated to each subject and Test, when 25 mg atomoxetine and 20 mg paroxetine were coadministered. Between the two periods, the volunteers received an oral daily dose of 20-40 mg paroxetine, for 6 days. Atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations were determined within the first 48 hours following drug administration. The pharmacokinetic parameters of both compounds were assessed using a non-compartmental method and the analysis of variance aimed at identifying any statistical significant differences between the pharmacokinetic parameters of atomoxetine and its main metabolite, corresponding to each study period.
  
  
  RESULTS
  Paroxetine modified the pharmacokinetic parameters of atomoxetine. Cmax increased from 221.26±94.93 to 372.53±128.28 ng/mL, while AUC0-t and AUC0-∞ also increased from 1151.19±686.52 to 6452.37±3388.76 ng*h/mL, and from 1229.15±751.04 to 7111.74±4195.17 ng*h/mL respectively. The main metabolite pharmacokinetics was also influenced by paroxetine intake, namely Cmax, AUC0-t and AUC0-∞ decreased from 688.76±270.27 to 131.01±100.43 ng*h/mL, and from 4810.93±845.06 to 2606.04±923.88 and from 4928.55±853.25 to 3029.82 ±941.84 respectively.
  
  
  CONCLUSIONS
  Multiple-dose paroxetine intake significantly influenced atomoxetine and its active metabolite pharmacokinetics, causing a 5.8-fold increased exposure to atomoxetine and 1.6-fold reduced exposure to 4-hydroxyatomoxetine-O-glucuronide.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Todor
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Adina
authors.initials: A
authors.lastname: Popa
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Neag
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Muntean
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Bocsan
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Buzoianu
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Gheldiu
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Chira
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Briciu
keywords: 4-hydroxyatomoxetine; atomoxetine; drug interaction; paroxetine; pharmacokinetics