title: Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.
abstract: To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers.
  
  
  
  An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods.
  
  
  
  Bupropion intake influenced all the pharmacokinetic parameters of both atomoxetine and its metabolite. For atomoxetine, Cmax increased from 226±96.1 to 386±137 ng/mL and more importantly, AUC0-∞ was significantly increasedfrom 1580±1040 to 8060±4160 ng*h/mL, while the mean t1/2 was prolonged after bupropion pretreatment. For 4-hydroxyatomoxetine-O-glucuronide, Cmax and AUC0-∞  were decreased from 707±269 to 212±145 ng/mL and from 5750±1240 to 3860±1220 ng*h/mL, respectively.
  
  
  
  These results demonstrated that the effect of bupropion on CYP2D6 activity was responsible for an increased systemic exposure to atomoxetine (5.1-fold) and also for a decreased exposure to its main metabolite (1.5-fold). Additional studies are required in order to evaluate the clinical relevance of this pharmacokinetic drug interaction.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
authors: University of Medicine and Pharmacy "Iuliu Hatieganu", Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania.
authors: Ioana
authors: I
authors: Todor
authors: Adina
authors: A
authors: Popa
authors: Maria
authors: M
authors: Neag
authors: Dana
authors: D
authors: Muntean
authors: Corina
authors: C
authors: Bocsan
authors: Anca
authors: A
authors: Buzoianu
authors: Laurian
authors: L
authors: Vlase
authors: Ana-Maria
authors: AM
authors: Gheldiu
authors: Corina
authors: C
authors: Briciu
mesh_terms: D000293:Adolescent; D000328:Adult; D000069445:Atomoxetine Hydrochloride / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D016642:Bupropion / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016642:Bupropion; D000069445:Atomoxetine Hydrochloride