INFLUENCE OF FLUVOXAMINE ON CARVEDILOL'S PHARMACOKINETICS IN RATS
MARIA BIANCA ABRUDAN 1, DANA MARIA MUNTEAN 1*, LAURIAN VLASE 1, ANA-MARIA GHELDIU 1, CRISTIAN BERCE 2, LAURENȚIU STOICESCU 3, MARIA ADRIANA NEAG 4
1Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, “Iuliu Hațieganu” University of
Medicine and Pharmacy, 41 Victor Babeș, Cluj-Napoca 400012, Romania
2Centre for Experimental Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 6 Louis Pasteur, Cluj-Napoca
400349, Romania
3Department of Cardiology, Vth Medical Clinic, Clinical Municipal Hospital, “Iuliu Hațieganu” University of Medicine and
Pharmacy, Faculty of Medicine, 11 Tăbăcarilor, Cluj-Napoca 400139, Romania
4Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, “Iuliu Hațieganu” University
of Medicine and Pharmacy, 41 Victor Babeș, Cluj-Napoca 400012, Romania
*corresponding author: dana.muntean@umfcluj.ro
Download Full Article

Abstract:
Carvedilol is one of the most used cardiovascular drugs, highly metabolized by CYP450 2D6, 1A2, 2C9. Fluvoxamine, an
antidepressant agent, is a moderate/potent inhibitor of these enzymes. There is the risk of drug-drug interaction when these
two drugs are concomitantly administered. The aim of this study was to investigate the drug-drug interactions between
carvedilol and fluvoxamine in rats. There were two periods: reference and test. In the first period each rat received an oral
dose of 3.57 mg/kg body weight carvedilol. In the test period, carvedilol was administered after a pre-treatment with
multiple oral doses of fluvoxamine (14.28 mg/kg b.w.). HPLC-MS was used to determine the plasma concentration of
carvedilol. The PK parameters were calculated by non-compartmental analysis. Fluvoxamine co-administered with carvedilol
can change the PK parameters (increase AUC, t1/2, decrease the Cl). The present study demonstrated the pharmacokinetic
drug-drug interaction between carvedilol and fluvoxamine in vivo.

Top