THE INFLUENCE OF SERTRALINE ON THE PHARMACOKINETICS
OF CARVEDILOL. A PRECLINICAL STUDY ON RATS
MARIA BIANCA ABRUDAN1, DANA MARIA MUNTEAN1*, MARIA ADRIANA NEAG2, LAURIAN VLASE1, ANA-MARIA GHELDIU1
1Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu Hațieganu” University of
Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012, Cluj-Napoca, Romania
2Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, “Iuliu Hațieganu” University
of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012, Cluj-Napoca, Romania
*corresponding author: dana.muntean@umfcluj.ro
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Abstract:
The objective of this study was to investigate the effect of multiple-dose sertraline on the pharmacokinetic profile of
carvedilol in rats. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) on the absence of sertraline or
after a pre-treatment with multiple oral doses of sertraline (7.14 mg/kg b.m.). The plasma concentrations of carvedilol were
estimated by HPLC-MS. After carvedilol co-administration with sertraline, an approximately 7.7-fold increase in the
exposure of carvedilol was observed, considering the significantly elevated value of AUC0-∞. Moreover, an increase by 250%
of peak plasma concentration was found, as well as an augmentation by 450% of the half life time of carvedilol was
observed. Sertraline co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these
effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.

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