Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats
<b>Background/Objectives</b>: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disor...
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2024-10-01
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| author | Iulia-Maria Ciocotișan Dana Maria Muntean Laurian Vlase |
| author_facet | Iulia-Maria Ciocotișan Dana Maria Muntean Laurian Vlase |
| author_sort | Iulia-Maria Ciocotișan |
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| description | <b>Background/Objectives</b>: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disorders, is known as a moderate or strong CYP2D6 enzyme inhibitor. This in vivo experiment aimed to assess the presence of a pharmacokinetic drug interaction between aripiprazole and bupropion and its magnitude on the systemic exposure of aripiprazole. <b>Methods</b>: 24 healthy <i>Wistar albino</i> male rats were included in two study groups. A single dose of 8 mg/kg aripiprazole was given to rats in the reference group, while the test group received repeated doses of bupropion for 6 days, followed by a single dose of aripiprazole. An LC-MS/MS method was developed for the concomitant quantification of aripiprazole and its active metabolite, dehydroaripiprazole, and non-compartmental analysis was employed to assess their pharmacokinetic parameters. <b>Results</b>: The mean AUC<sub>0-∞</sub> of aripiprazole increased 5.65-fold (1117.34 ± 931.41 vs. 6311.66 ± 2978.71 hr·ng/mL), the mean C<sub>max</sub> increased by 96.76% and the apparent systemic clearance decreased over 9-fold after bupropion repeated doses. The exposure to aripiprazole’s active metabolite increased as well, having a 4-fold increase in the mean AUC<sub>0–∞</sub> (from 461.13 ± 339.82 to 1878.66 ± 1446.91 hr·ng/mL) and a 2-fold increase in the mean C<sub>max</sub>. <b>Conclusions</b>: The total exposure to the aripiprazole parent compound and active moiety significantly increased after bupropion pretreatment in this preclinical in vivo experiment. Clinical studies should further establish the significance of this interaction in humans. |
| format | Article |
| id | doaj-art-41c8912c74e6489ebf33413dfe812936 |
| institution | Kabale University |
| issn | 2218-1989 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Metabolites |
| spelling | doaj-art-41c8912c74e6489ebf33413dfe8129362024-11-26T18:13:05ZengMDPI AGMetabolites2218-19892024-10-01141158810.3390/metabo14110588Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> RatsIulia-Maria Ciocotișan0Dana Maria Muntean1Laurian Vlase2Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, RomaniaDepartment of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, RomaniaDepartment of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania<b>Background/Objectives</b>: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disorders, is known as a moderate or strong CYP2D6 enzyme inhibitor. This in vivo experiment aimed to assess the presence of a pharmacokinetic drug interaction between aripiprazole and bupropion and its magnitude on the systemic exposure of aripiprazole. <b>Methods</b>: 24 healthy <i>Wistar albino</i> male rats were included in two study groups. A single dose of 8 mg/kg aripiprazole was given to rats in the reference group, while the test group received repeated doses of bupropion for 6 days, followed by a single dose of aripiprazole. An LC-MS/MS method was developed for the concomitant quantification of aripiprazole and its active metabolite, dehydroaripiprazole, and non-compartmental analysis was employed to assess their pharmacokinetic parameters. <b>Results</b>: The mean AUC<sub>0-∞</sub> of aripiprazole increased 5.65-fold (1117.34 ± 931.41 vs. 6311.66 ± 2978.71 hr·ng/mL), the mean C<sub>max</sub> increased by 96.76% and the apparent systemic clearance decreased over 9-fold after bupropion repeated doses. The exposure to aripiprazole’s active metabolite increased as well, having a 4-fold increase in the mean AUC<sub>0–∞</sub> (from 461.13 ± 339.82 to 1878.66 ± 1446.91 hr·ng/mL) and a 2-fold increase in the mean C<sub>max</sub>. <b>Conclusions</b>: The total exposure to the aripiprazole parent compound and active moiety significantly increased after bupropion pretreatment in this preclinical in vivo experiment. Clinical studies should further establish the significance of this interaction in humans.https://www.mdpi.com/2218-1989/14/11/588pharmacokineticsinteraction studiesmetabolismaripiprazoledehydroaripiprazolebupropion |
| spellingShingle | Iulia-Maria Ciocotișan Dana Maria Muntean Laurian Vlase Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats Metabolites pharmacokinetics interaction studies metabolism aripiprazole dehydroaripiprazole bupropion |
| title | Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats |
| title_full | Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats |
| title_fullStr | Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats |
| title_full_unstemmed | Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats |
| title_short | Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in <i>Wistar albino</i> Rats |
| title_sort | bupropion increased more than five times the systemic exposure to aripiprazole an in vivo study in i wistar albino i rats |
| topic | pharmacokinetics interaction studies metabolism aripiprazole dehydroaripiprazole bupropion |
| url | https://www.mdpi.com/2218-1989/14/11/588 |
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