Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats

Abstract

1. The aim of the present study was to investigate the effect of naringenin (4,5,7-trihydroxy flavonone) on the pharmacokinetics of metoprolol, a substrate of Cytochrome P-450 3A4 (CYP3A4), CYP2C9, and CYP2D6 in rats.

2. Male Wistar rats were treated orally with metoprolol (30 mg/kg) alone and in combination with naringenin (25, 50, and 100 mg/kg) once daily for 15 consecutive days.

3. The plasma concentrations of metoprolol were determined using Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) on the 1st day in single-dose pharmacokinetic (PK) study (SDS) and on the 15th day in multiple dosing PK studies (MDS).

4. Compared to the metoprolol control group, the C_max, AUC, and half-life (T_1/2) of metoprolol increased in rats pre-treated with naringenin, while there was no significant change in T_max. There is a significant decrease in clearance and volume of distribution.

5. The present study results revealed that naringenin significantly enhanced the C_max, AUC, MRT, t_1/2, and decreased the clearance of metoprolol possibly through the inhibition of CYP enzymes involved in the metabolism of metoprolol.

Keywords:

• Metoprolol
• Naringenin
• CYP2D6
• CYP3A4
• CYP2C9
• bioavailability
• pharmacokinetics

Acknowledgements

The authors are grateful to Vignan’s Foundation for Science, Technology, and Research (Deemed to be University), Vadlamudi, and KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, for providing necessary facilities and their encouragement in completing this work.

Disclosure statement

The authors declare that this research does not have any conflict of interest with anyone or any Institute.