Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers

Authors

  • Ioana Todor University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania
  • Adina Popa University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Clinical Pharmacy, Cluj-Napoca, Romania
  • Maria Neag University of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, Romania
  • Dana Muntean University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania
  • Corina Bocsan University of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, Romania
  • Anca Buzoianu University of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, Romania
  • Laurian Vlase University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania
  • Ana-Maria Gheldiu University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania
  • Corina Briciu University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Clinical Pharmacy, Cluj-Napoca, Romania

DOI:

https://doi.org/10.18433/J3H03R

Abstract

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.

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Published

2016-06-15

How to Cite

Todor, I., Popa, A., Neag, M., Muntean, D., Bocsan, C., Buzoianu, A., … Briciu, C. (2016). Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers. Journal of Pharmacy & Pharmaceutical Sciences, 19(2), 198–207. https://doi.org/10.18433/J3H03R

Issue

Section

Pharmaceutical Sciences; Review Articles