Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study

Authors

  • Maria Bianca Abrudan
  • Daniela Saveta Popa
  • Dana Maria Muntean
  • Ana Maria Gheldiu
  • Laurian Vlase

DOI:

https://doi.org/10.15386/mpr-1225

Keywords:

pharmacokinetics, CYP2D6, rat liver microsomes, carvedilol, antidepressants

Abstract

Background and aims. Cardiovascular diseases and depressive disorders are some of the most frequent diseases. The probability of concomitant prescription of antihypertensive and antidepressive medication is increasing. The aim of this study was to investigate the enzyme inhibition by bupropion, sertraline and fluvoxamine on the metabolism of carvedilol using rat pooled liver microsomes and to assess the importance of these interactions from the pharmacokinetic mechanism point of view.

Methods. Two substrate concentrations (0.5 and 1 μM) and four inhibitor concentrations (0, 0.1, 0.75 and 1.5 μM) were used for each tested inhibitor.

Results. The results of the in vitro experiments showed a significant decrease of the metabolic rate of carvedilol to 4'-hydroxyphenyl carvedilol, for all tested inhibitors, when the inhibitor was added to the incubation mixture containing the substrate. Moreover, an increase of the area under the concentration-time curve for carvedilol was observed after incubation with each  tested inhibitor compared with the control state (no inhibitor). The most potent inhibitor was sertraline, followed by fluvoxamine and bupropion.

Conclusion. The co-administration of tested antidepressants led to a significant alteration of carvedilol’s metabolism in vitro. CYP2D6 inhibition is the main pharmacokinetic mechanism that can explain these drug-drug interactions, with possible clinical implications.

Author Biographies

Maria Bianca Abrudan, "Iuliu Hatieganu" University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania

Department of Pharmaceutical Technology and Biopharmacy

Daniela Saveta Popa, "Iuliu Hatieganu" University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania

Department of Toxicology

Dana Maria Muntean, "Iuliu Hatieganu" University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania

Department of Pharmaceutical Technology and Biopharmacy

Ana Maria Gheldiu, "Iuliu Hatieganu" University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania

Department of Pharmaceutical Technology and Biopharmacy

Laurian Vlase, "Iuliu Hatieganu" University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania

Department of Pharmaceutical Technology and Biopharmacy

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Published

2019-04-23

How to Cite

1.
Abrudan MB, Popa DS, Muntean DM, Gheldiu AM, Vlase L. Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study. Med Pharm Rep [Internet]. 2019 Apr. 23 [cited 2025 Oct. 5];92(2):158-64. Available from: https://medpharmareports.com/index.php/mpr/article/view/1225

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Section

Original Research