Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers
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 f...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-06-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/27691 |
| _version_ | 1827162356598177792 |
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| author | Ioana Todor Adina Popa Maria Neag Dana Muntean Corina Bocsan Anca Buzoianu Laurian Vlase Ana-Maria Gheldiu Corina Briciu |
| author_facet | Ioana Todor Adina Popa Maria Neag Dana Muntean Corina Bocsan Anca Buzoianu Laurian Vlase Ana-Maria Gheldiu Corina Briciu |
| author_sort | Ioana Todor |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T04:50:07Z |
| format | Article |
| id | doaj.art-9f0d27b7f261436393225543e967ed1b |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2025-03-21T00:43:31Z |
| publishDate | 2016-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-9f0d27b7f261436393225543e967ed1b2024-08-03T06:01:01ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262016-06-0119210.18433/J3H03REvaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy VolunteersIoana Todor0Adina Popa1Maria Neag2Dana Muntean3Corina Bocsan4Anca Buzoianu5Laurian Vlase6Ana-Maria Gheldiu7Corina Briciu8University of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Clinical Pharmacy, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy, "Iuliu Hatieganu”, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, RomaniaUniversity of Medicine and Pharmacy “Iuliu Hatieganu”, Faculty of Pharmacy, Department of Clinical Pharmacy, Cluj-Napoca, RomaniaPurpose: 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.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/27691 |
| spellingShingle | Ioana Todor Adina Popa Maria Neag Dana Muntean Corina Bocsan Anca Buzoianu Laurian Vlase Ana-Maria Gheldiu Corina Briciu Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers Journal of Pharmacy & Pharmaceutical Sciences |
| title | Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers |
| title_full | Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers |
| title_fullStr | Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers |
| title_full_unstemmed | Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers |
| title_short | Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers |
| title_sort | evaluation of a potential metabolism mediated drug drug interaction between atomoxetine and bupropion in healthy volunteers |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/27691 |
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