Open AccessEvaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers
Author(s) -
Ioana Todor,
Adina Popa,
Maria Adriaeag,
Dana Muntean,
Ioana Corina Bocșan,
Anca Dana Buzoianu,
Laurian Vlase,
Ana-Maria Gheldiu,
Corina Briciu
Publication year - 2016
Publication title -
journal of pharmacy and pharmaceutical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.497
H-Index - 78
ISSN - 1482-1826
DOI - 10.18433/j3h03r
Subject(s) - atomoxetine , bupropion , drug , pharmacology , drug metabolism , medicine , drug drug interaction , drug interaction , methylphenidate , psychiatry , attention deficit hyperactivity disorder , smoking cessation , pathology
Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.